High PD-L1 expression indicates poor prognosis of HIV-infected patients with non-small cell lung cancer

Abstract

Background

The status of antitumor immunity represented by the expression of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) and immune cell (IC) infiltration is unknown in HIV-infected patients with non-small cell lung cancer (NSCLC).

Methods

Fifteen HIV-infected patients with NSCLC were compared with 29 non-HIV-infected patients with NSCLC. Analysis of 13 propensity-score-matched patients in the two groups was also compared. The expression of PD-1/PD-L1 and tumor infiltration by CD4⁺, CD8⁺, and CD56⁺ immune cells were examined by immunohistochemistry; score of ≥ 2 was defined as positive.

Results

Although high PD-L1 expression in tumor cells was observed in HIV and non-HIV cohorts, the association of PD-1/PD-L1 was significant only in the HIV cohort. In overall as well as the propensity-matched analyses, HIV-infected patients with high PD-L1 expression showed shorter survival than HIV-infected patients with low PD-L1 expression; no significant difference was observed in this respect in the non-HIV cohort.

Conclusion

High PD-L1 expression in tumor tissue was associated with poor prognosis in HIV-infected NSCLC patients but not in non-HIV-infected NSCLC patients. These results suggest that antitumor immunity by PD-1/PD-L1 axis might be suppressed more in HIV-infected NSCLC patients as compared to their non-HIV-infected counterparts.

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Resuscitative endovascular balloon occlusion of the aorta may increase the bleeding of minor thoracic injury in severe multiple trauma patients: a case report

The resuscitative endovascular balloon occlusion of the aorta, because of its efficacy and feasibility, has been widely used in treating patients with severe torso trauma. However, complications developing aro...

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Considerations in Setting Up and Planning a Graft Processing Facility

Publication date: Available online 13 December 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Mickey B.C. Koh




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Corrigendum to “A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma – A final report” [Eur J of Canc (2017) 206–225]

Publication date: Available online 14 December 2017
Source:European Journal of Cancer
Author(s): Astrid K. Gnekow, David A. Walker, Daniela Kandels, Susan Picton, Giorgio Perilongo, Jacques Grill, Tore Stokland, Per Eric Sandstrom, Monika Warmuth-Metz, Torsten Pietsch, Felice Giangaspero, René Schmidt, Andreas Faldum, Denise Kilmartin, Angela De Paoli, Gian Luca De Salvo




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Radium-223 international early access program: results from the Spanish subset

Future Oncology, Ahead of Print.


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Validation of the eighth clinical American Joint Committee on Cancer stage grouping for esophageal cancer

Future Oncology, Ahead of Print.


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Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia

Future Oncology, Ahead of Print.


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First-decade patient with colorectal cancer carrying both germline and somatic mutations in APC gene

Abstract

Background

Colorectal carcinoma (CRC) is one of the most common causes of cancer-related deaths. The mean age of patients with CRC ranges from 49 to 60 years. Pediatric CRC is unusual, which often escapes early diagnosis because of a lack of awareness of its occurrence in children. The association between the mutation of APC and the occurrence of CRC in the first decade of life remains unknown.

Case presentation

We report a 10-year-old child with CRC; he was diagnosed with stage IIIB advanced transverse colon cancer without distal metastases. We detected a heterozygous germline mutation at c.5465 T > A in both blood and tissue samples and a heterozygous somatic mutation at c.7397C > T in the tissue sample. Both of these mutations can cause CRC tumorigenesis in the first decade of life.

Conclusions

The rare genetic features of this 10-year-old patient might be the predisposing cause of pediatric CRC. Therefore, screening patients with early-onset CRC through clinical and genetic characterizations is suggested.

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Validation of the eighth clinical American Joint Committee on Cancer stage grouping for esophageal cancer

Future Oncology, Ahead of Print.


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Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia

Future Oncology, Ahead of Print.


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First-decade patient with colorectal cancer carrying both germline and somatic mutations in APC gene

Abstract

Background

Colorectal carcinoma (CRC) is one of the most common causes of cancer-related deaths. The mean age of patients with CRC ranges from 49 to 60 years. Pediatric CRC is unusual, which often escapes early diagnosis because of a lack of awareness of its occurrence in children. The association between the mutation of APC and the occurrence of CRC in the first decade of life remains unknown.

Case presentation

We report a 10-year-old child with CRC; he was diagnosed with stage IIIB advanced transverse colon cancer without distal metastases. We detected a heterozygous germline mutation at c.5465 T > A in both blood and tissue samples and a heterozygous somatic mutation at c.7397C > T in the tissue sample. Both of these mutations can cause CRC tumorigenesis in the first decade of life.

Conclusions

The rare genetic features of this 10-year-old patient might be the predisposing cause of pediatric CRC. Therefore, screening patients with early-onset CRC through clinical and genetic characterizations is suggested.

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Preclinical evaluation of SCC244 (Glumetinib), a novel, potent and highly selective inhibitor of c-Met in MET-dependent cancer models

Because the receptor tyrosine kinase c-Met plays a critical role in tumor growth, metastasis, tumor angiogenesis and drug resistance, the c-Met axis represents an attractive therapeutic target. Herein, we report the first preclinical characterization of SCC244, a novel, potent and highly selective inhibitor of c-Met kinase. SCC244 showed subnanomolar potency against c-Met kinase activity and high selectivity versus 312 other tested protein kinases, making it one of the most selective c-Met inhibitors described to date. Moreover, this inhibitor profoundly and specifically inhibits c-Met signal transduction and thereby suppresses the c-Met-dependent neoplastic phenotype of tumor and endothelial cells. In xenografts of human tumor cell lines or non-small-cell lung cancer and hepatocellular carcinoma patient-derived tumor tissue driven by MET aberration, SCC244 administration exhibits robust antitumor activity at the well-tolerated doses. Additionally, the in vivo antitumor activity of SCC244 involves the inhibition of c-Met downstream signaling via a mechanism of combined anti-proliferation and antiangiogenic effects. The results of the current study provide a strong foundation for the clinical investigation of SCC244 in patients with tumors harboring c-Met pathway alterations.

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Inhibiting Nuclear Phospho-Progesterone Receptor Enhances Antitumor Activity of Onapristone in Uterine Cancer

While progesterone receptor (PR)-targeted therapies are modestly active in patients with uterine cancer, their underlying molecular mechanisms are not well understood. The clinical use of such therapies is limited because of the lack of biomarkers that predict response to PR-agonists (progestins) or PR-antagonists (onapristone). Thus, understanding the underlying molecular mechanisms of action will provide an advance in developing novel combination therapies for cancer patients. Nuclear translocation of PR has been reported to be ligand-dependent or -independent. Here, we identified that onapristone, a PR antagonist, inhibited nuclear translocation of ligand-dependent or -independent (EGF) phospho-PR (S294), while trametinib inhibited nuclear translocation of EGF induced phospho-PR (S294). Using orthotopic mouse models of uterine cancer, we demonstrated that the combination of onapristone and trametinib results in superior anti-tumor effects in uterine cancer models compared to either monotherapy. These synergistic effects are, in part, mediated through inhibiting the nuclear translocation of EGF induced PR phosphorylation in uterine cancer cells. Targeting MAPK-dependent PR activation with onapristone and trametinib, significantly inhibited tumor growth in preclinical uterine cancer models and is worthy of further clinical investigation.

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Preclinical evaluation of SCC244 (Glumetinib), a novel, potent and highly selective inhibitor of c-Met in MET-dependent cancer models

Because the receptor tyrosine kinase c-Met plays a critical role in tumor growth, metastasis, tumor angiogenesis and drug resistance, the c-Met axis represents an attractive therapeutic target. Herein, we report the first preclinical characterization of SCC244, a novel, potent and highly selective inhibitor of c-Met kinase. SCC244 showed subnanomolar potency against c-Met kinase activity and high selectivity versus 312 other tested protein kinases, making it one of the most selective c-Met inhibitors described to date. Moreover, this inhibitor profoundly and specifically inhibits c-Met signal transduction and thereby suppresses the c-Met-dependent neoplastic phenotype of tumor and endothelial cells. In xenografts of human tumor cell lines or non-small-cell lung cancer and hepatocellular carcinoma patient-derived tumor tissue driven by MET aberration, SCC244 administration exhibits robust antitumor activity at the well-tolerated doses. Additionally, the in vivo antitumor activity of SCC244 involves the inhibition of c-Met downstream signaling via a mechanism of combined anti-proliferation and antiangiogenic effects. The results of the current study provide a strong foundation for the clinical investigation of SCC244 in patients with tumors harboring c-Met pathway alterations.

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Molecularly Targeted Cancer Combination Therapy with Near Infrared Photoimmunotherapy and Near Infrared Photo-release with Duocarmycin-antibody Conjugate.

Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). However, the effect of NIR-PIT can be enhanced when combined with other therapies. NIR photocaging groups, based on the heptamethine cyanine scaffold, have been developed to release bioactive molecules near targets after exposure to light. Here, we investigated the combination of NIR-PIT employing panitumumab-IR700 (pan-IR700) and the NIR-releasing compound, CyEt-Panitumumab-Duocarmycin (CyEt-Pan-Duo). Both pan-IR700 and CyEt-Pan-Duo showed specific binding to the EGFR-expressing MDAMB468 cell line in vitro. In in vivo studies, additional injection of CyEt-Pan-Duo immediately after NIR light exposure resulted in high tumor accumulation and high tumor-background ratio. To evaluate the effects of combination therapy in vivo, tumor-bearing mice were separated into 4 groups: (1) control; (2) NIR-PIT; (3) NIR-release; (4) combination of NIR-PIT and NIR-release. Tumor growth was significantly inhibited in all treatment groups compared with the control group (p < 0.05), and significantly prolonged survival was achieved (p < 0.05 vs control). The greatest therapeutic effect was shown with NIR-PIT and NIR-release combination therapy. In conclusion, combination therapy of NIR-PIT and NIR-release enhanced the therapeutic effects compared with either NIR-PIT or NIR-release therapy alone.

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Inhibiting Nuclear Phospho-Progesterone Receptor Enhances Antitumor Activity of Onapristone in Uterine Cancer

While progesterone receptor (PR)-targeted therapies are modestly active in patients with uterine cancer, their underlying molecular mechanisms are not well understood. The clinical use of such therapies is limited because of the lack of biomarkers that predict response to PR-agonists (progestins) or PR-antagonists (onapristone). Thus, understanding the underlying molecular mechanisms of action will provide an advance in developing novel combination therapies for cancer patients. Nuclear translocation of PR has been reported to be ligand-dependent or -independent. Here, we identified that onapristone, a PR antagonist, inhibited nuclear translocation of ligand-dependent or -independent (EGF) phospho-PR (S294), while trametinib inhibited nuclear translocation of EGF induced phospho-PR (S294). Using orthotopic mouse models of uterine cancer, we demonstrated that the combination of onapristone and trametinib results in superior anti-tumor effects in uterine cancer models compared to either monotherapy. These synergistic effects are, in part, mediated through inhibiting the nuclear translocation of EGF induced PR phosphorylation in uterine cancer cells. Targeting MAPK-dependent PR activation with onapristone and trametinib, significantly inhibited tumor growth in preclinical uterine cancer models and is worthy of further clinical investigation.

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Anti-Tumor Activity of Entrectinib, a Pan-TRK, ROS1 and ALK Inhibitor, in ETV6-NTRK3-Positive Acute Myeloid Leukemia

Activation of tropomyosin receptor kinase (TRK) family tyrosine kinases by chromosomal rearrangement has been shown to drive a wide range of solid tumors and hematologic malignancies. TRK fusions are actionable targets as evidenced by recent clinical trial results in solid tumors. Entrectinib (RXDX-101) is an investigational, orally available, CNS-active, highly potent and selective kinase inhibitor against TRKA/B/C, ROS1 and ALK kinase activities. Here, we demonstrate that TRK kinase inhibition by entrectinib selectively targets preclinical models of TRK fusion-driven hematologic malignancies. In acute myeloid leukemia (AML) cell lines with endogenous expression of the ETV6-NTRK3 fusion gene, entrectinib treatment blocked cell proliferation and induced apoptotic cell death in vitro with sub-nanomolar IC50 values. Phosphorylation of the ETV6-TRKC fusion protein and its downstream signaling effectors was inhibited by entrectinib treatment in a dose-dependent manner. In animal models, entrectinib treatment at clinically relevant doses resulted in tumor regression that was accompanied by elimination of residual cancer cells from the bone marrow. Our preclinical data demonstrate the potential of entrectinib as an effective treatment for patients with TRK fusion-driven AML and other hematologic malignancies.

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Phase 1 dose-escalation study of anti CTLA-4 antibody ipilimumab and lenalidomide in patients with advanced cancers

Preclinical data suggest that combining a check point inhibition with immunomodulatory derivative can increase anticancer response. We designed a dose escalation study using a 3+3 design to determine the safety, maximum tolerated dose (MTD) or recommended phase 2 dose (R2PD) and dose limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3mg/kg intravenously every 28 days x 4) and lenalidomide (10-25mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity) in advanced cancers. Total of 36 patients (Hodgkin lymphoma, 7; melanoma, 5; leiomyosarcoma, 4; renal cancer, 3; thyroid cancer, 3; other cancers, 14; median of 3 prior therapies) were enrolled. The MTD has not been reached and ipilimumab 3mg/kg and lenalidomide 25 mg have been declared as R2PD. DLT were grade (G) 3 rash (3 patients) and G3 pancreatitis (1 patient). G3/4 drug related toxicities other than DLT were G3 anemia (5 patients), G3 thromboembolism (2 patients), G3 thrombocytopenia, rash, hypopituitarism, G3 pneumonitis, G3 transaminitis and G4 hypopituitarism (all in 1 patient). Eight patients had tumor shrinkage per immune-related response criteria (-79% to -2%) including a PR (-79% for 7.2+ months) in a refractory Hodgkin lymphoma. Using comprehensive genomic profiling a total mutation burden (mutations/Mb) was evaluated in 17 patients, with one of the patients achieving a PR demonstrated intermediate mutation burden. In conclusion, combination of ipilimumab and lenalidomide is well tolerated and demonstrated preliminary signals of activity in patients with refractory Hodgkin lymphoma and other advanced cancers.

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Use of PRO measures to inform tolerability in oncology trials: Implications for clinical review, IND safety reporting and clinical site inspections

Cancer therapeutics frequently lead to symptomatic adverse events (AEs) that can affect treatment tolerability. The National Cancer Institute has developed a patient-reported outcome (PRO) version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to assess symptomatic AEs by direct patient self-report. While longitudinal assessment of patient-reported symptomatic AEs holds promise to better inform treatment tolerability, using PRO measures to assess symptomatic AEs has raised several regulatory and good clinical practice (GCP) issues among those who conduct cancer clinical trials. These include concerns regarding trial monitoring, clinical review of PRO results by investigators and delegated clinical staff, whether PRO data on symptomatic AEs require IND safety reporting, and how the trial conduct and resultant PRO data will be assessed during clinical investigator site inspections. This article addresses current thinking regarding these issues in cancer clinical trials from the Food and Drug Administration, the National Cancer Institute and the Office for Human Research Protections. PRO measures such as PRO-CTCAE that assess symptomatic AEs in cancer trials are considered similar to other PRO assessments of symptoms, function and health-related quality of life, and can generate complementary data that may inform tolerability. Clarity on operational concerns related to incorporating PRO measures to inform tolerability is critical to continue the advancement of rigorous PRO assessment in cancer clinical trials.

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Use of PRO measures to inform tolerability in oncology trials: Implications for clinical review, IND safety reporting and clinical site inspections

Cancer therapeutics frequently lead to symptomatic adverse events (AEs) that can affect treatment tolerability. The National Cancer Institute has developed a patient-reported outcome (PRO) version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to assess symptomatic AEs by direct patient self-report. While longitudinal assessment of patient-reported symptomatic AEs holds promise to better inform treatment tolerability, using PRO measures to assess symptomatic AEs has raised several regulatory and good clinical practice (GCP) issues among those who conduct cancer clinical trials. These include concerns regarding trial monitoring, clinical review of PRO results by investigators and delegated clinical staff, whether PRO data on symptomatic AEs require IND safety reporting, and how the trial conduct and resultant PRO data will be assessed during clinical investigator site inspections. This article addresses current thinking regarding these issues in cancer clinical trials from the Food and Drug Administration, the National Cancer Institute and the Office for Human Research Protections. PRO measures such as PRO-CTCAE that assess symptomatic AEs in cancer trials are considered similar to other PRO assessments of symptoms, function and health-related quality of life, and can generate complementary data that may inform tolerability. Clarity on operational concerns related to incorporating PRO measures to inform tolerability is critical to continue the advancement of rigorous PRO assessment in cancer clinical trials.

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Clinical and Genetic Implications of DNA Mismatch Repair Deficiency in Biliary Tract Cancers Associated with Lynch Syndrome

Abstract

Purpose

Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS.

Methods

A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2.

Results

Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months.

Conclusions

dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.

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Clinical and Genetic Implications of DNA Mismatch Repair Deficiency in Biliary Tract Cancers Associated with Lynch Syndrome

Abstract

Purpose

Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS.

Methods

A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2.

Results

Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months.

Conclusions

dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.

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Linc-ROR promotes esophageal squamous cell carcinoma progression through the derepression of SOX9

Novel therapies tailored to the molecular composition of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. We investigated the regulatory network of long intergenic non-protein ...

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Adipocytes promote cholangiocarcinoma metastasis through fatty acid binding protein 4

The early occurrence regional nodal and distant metastases cholangiocarcinoma (CCA) is one of the major reasons for its poor prognosis. However, the related mechanisms are largely elusive. Recently, increasing...

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CTCs May Predict Breast Cancer Recurrence [News in Brief]

Detection of CTCs in patients with ER-positive disease linked with nearly 22-fold increase in late recurrence risk.

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Anti-PD-1 Therapy OK for Most with HIV [News in Brief]

Early pembrolizumab data support inclusion of patients with HIV in oncology drug trials.

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Choroidal metastases as the presenting feature of adenocarcinoma of the lung: A case report and an overview of the role of radiotherapy in its management

Krishna Sharan, S Shailaja, Vijaya H Pai, Donald J Fernandes

Journal of Cancer Research and Therapeutics 2017 13(6):1062-1064

Although metastasis to the eye is the most common ophthalmic malignancy, it is usually asymptomatic and rarely a presenting symptom that leads to the diagnosis of a primary. Here, we report a patient who was evaluated for visual symptoms and was eventually diagnosed to have disseminated adenocarcinoma of the lung. He was treated with external radiotherapy to the choroidal metastasis, attaining an excellent response that was sustained until his death. A brief review on the role of radiotherapy in the management of uveal metastases is also presented.

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Expression of WW domain-containing protein 2 is correlated with pathological grade and recurrence of glioma

Jun Liang, Wei-Feng Qi, Shao Xie, Wei-Feng Wang, Xian-Li Zhang, Xiu-Ping Zhou, Qiong-Shi , Jin-Xia Hu, Ru-Tong Yu

Journal of Cancer Research and Therapeutics 2017 13(6):1032-1037

Objective: WW domain-containing protein 2 (WWP2) is an E3 ubiquitin ligase, which belongs to the NEDD4-like protein family. Recently, it is reported to play a key role in tumorigenesis and development of tumors such as prostate and lung cancer. However, there has been not related report on glioma until now. The aim of this study is to detect the expression of WWP2 and analyze its correlation to the pathological grade and tumor recurrence in patients with glioma. Materials and Methods: Western blot and immunohistochemistry were separately used to detect the expression of WWP2 protein in 31 brain glioma tissue samples and 80 brain glioma paraffin specimens. The method of Kaplan–Meier was used to analyze the correlation between the WWP2 expression and glioma recurrence. Results: The protein expression level of WWP2 in glioma tissue was significantly higher than that in nontumorous brain tissue (P < 0.05), and the protein expression level of WWP2 in high-grade glioma (Grade III–IV) was significantly higher than that in low-grade glioma (Grade I–II) (P < 0.05). Kaplan–Meier analysis indicated that the patients with high WWP2 expression had significantly shorter tumor recurrence time than the patients with low WWP2 expression (P < 0.05). Conclusion: Our study suggests that WWP2 may play a role in the genesis and development of glioma; it may be a potential biomarker to predict pathological grade and tumor recurrence in patients with glioma.

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Occupational doses of cardiologists in cath labs and simulation method

Reza Fardid, Fatemeh Mirzadeh, Hadi Rezaei

Journal of Cancer Research and Therapeutics 2017 13(6):901-907

In recent years, using the ionizing radiation in the interventional cardiology has been increased; this is because of the rapid growth of the number of interventional procedures and the high levels of radiation dose in these examinations. Therefore, it is necessary to develop procedures for managing the use of fluoroscopy radiation to ensure that patients and personnel are not exposed to excessive levels of radiation. It seems that by the new generation devices of fluoroscopy that are equipped with a real dosimeters or dose area product (DAP)-meter which are able to record the produced dose rate in the area of patient's body in each procedure, it is possible to calculate the cardiologist dose with simulation. In addition, a relationship can be made between the patient DAP and cardiologist dose that is defined as an appropriate conversion factor. Hence, in each procedure, besides the record of patient's DAP, the cardiologist dose is recorded as well.

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Extramedullary sarcomatoid variant of plasmablastic plasmacytoma

Urmila Majhi, Shirley Sundersingh, Kanchan Murhekar, Krishnamurthy Radha

Journal of Cancer Research and Therapeutics 2017 13(6):1078-1079



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Optical diagnostics in oral cancer: An update on Raman spectroscopic applications

Aditi Sahu, C Murali Krishna

Journal of Cancer Research and Therapeutics 2017 13(6):908-915

Raman spectroscopy (RS) is a sensitive vibrational spectroscopic method that can detect even subtle biochemical changes during the onset of disease. Consequently, RS has been extensively investigated for disease diagnosis, including cancers. Oral cancers are known to suffer from dismal survival rates, which have not improved for several decades. As delayed diagnosis contributes to the low disease-free survival rate observed in oral cancers, RS has also been explored for the early diagnosis of oral cancers. This review summarizes the major developments in the field, including diagnosis, surgical margin assessment and prediction of treatment response, and in the overall management of oral cancers. The article comprises an overview of epidemiology, diagnosis, treatment, and recently introduced diagnostic adjuncts for oral cancers, the basic principle, instrumentation of RS, multivariate analysis that impart objectivity to the approach, and finally a discussion on the recent applications in oral cancers. PubMed and Google Scholar database have been used to compile information available online till December 2015.

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Neurofibromatosis type-1 in a patient with ataxia-telangiectasia

Serhan Kupeli

Journal of Cancer Research and Therapeutics 2017 13(6):1073-1074



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Quantitative determination of tumor platinum concentration of patients with advanced Breast, lung, prostate, or colorectal cancers undergone platinum-based chemotherapy

Hesameddin Mostaghimi, Ali Reza Mehdizadeh, Mohammad Jahanbakhsh, Amir Reza Dehghanian, Ramin Askari

Journal of Cancer Research and Therapeutics 2017 13(6):930-935

Context: Previous studies have reported direct relationship between tumor reduction and its platinum concentration following platinum-based (Pt-based) chemotherapy. However, quantitative data of tumor platinum concentration have not yet been reported for the most common cancers. Aims: Determination of tumor platinum concentration of breast, lung, prostate, and colorectal cancers after Pt-based chemotherapy; and evaluation of the influence of chemo drug type, chemotherapy regimen, and time lapse from last chemotherapy on tumor platinum concentration. Materials and Methods: Tumor samples of patients with advanced breast, lung, prostate, and colorectal cancers undergone Pt-based chemotherapy were collected from pathology collection of various hospitals. The platinum concentration of each sample was measured by inductively coupled plasma optical emission spectrometry. The data were categorized by drug type, time lapse from last chemotherapy, and regimen type to evaluate their effects on platinum concentration. Statistical Analysis: ANOVA, Mann–Whitney U and Kruskal–Wallis tests were used. Results: Tumor platinum concentrations of breast, lung, prostate, and colorectal cancers were all obtained in the range of 1–10 μg/g tumor tissue. Large values of P (>0.05) indicate no significant differences between various chemo drug, regimen, and time groups. Conclusions: In general, the platinum concentration was higher in prostate and lower in lung tumors. The type of Pt-based chemo drug, time lapse from the last chemotherapy, and concurrency of other antineoplastic agents administered with Pt-based chemo drugs had no significant effect on tumor platinum concentration.

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Agreement analysis between three different short geriatric screening scales in patients undergoing chemotherapy for solid tumors

Amit Joshi, Nidhi Tandon, Vijay M Patil, Vanita Noronha, Sudeep Gupta, Atanu Bhattacharjee, Kumar Prabhash

Journal of Cancer Research and Therapeutics 2017 13(6):1023-1026

Background: Comprehensive geriatric assessment (CGA) in routine practice is not logistically feasible. Short geriatric screening tools are available for selecting patients for CGA. However none of them is validated in India. In this analysis we aim to compare the level of agreement between three commonly used short screening tools (Flemish version of TRST (fTRST), G8 and VES-13. Methods: Patients ≥65 years with a solid tumor malignancy undergoing cancer directed treatment were interviewed between March 2013 to July 2014. Geriatric screening with G8, fTRST and VES-13 tools was performed in these patients. G8 score ≤14, fTRST score ≥1 and VES-13 score ≥3 were taken as indicators for the presence of a high risk geriatric profile respectively. R version 3.1.2 was used for analysis. Cohen kappa agreement statistics was used to compare the agreement between the 3 tools. p value of 0.05 was taken as significant. Results: The kappa statistics value for agreement between G8 score and fTRST, between VES-13 and fTRST and between VES-13 and G8 were 0.12 (P = 0.04), 0.16 (P = 0.07) and 0.05 (P = 0.45) respectively. It was found that maximum agreement was observed for VES-13 and fTRST. The agreement value of VES-13 and fTRST observed was 59.44 %(39.63% for high risk profile and 19.81% for low risk profile). The agreement value of G-8 and fTRST was 39.62% (2.83% only for high risk profile and 36.79% for low risk profile). The lowest agreement was between G8 and VES-13, 35.84% (7.54% for high risk detection and 28.30% for low risk detection). Conclusion: There was poor agreement (in view of kappa value been below 0.2) between the 3 short geriatric screening tools. Research needs to be directed to compare the agreement level between these 3 scales and CGA, so that the appropriate short screening tool can be selected for routine use.

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Assessment of the scatter correction procedures in single photon emission computed tomography imaging using simulation and clinical study

Mehravar Rafati, Hemmatollah Rouhani, Ahmad Bitarafan-Rajabi, Mahsa Noori-Asl, Bagher Farhood, Hadi Taleshi Ahangari

Journal of Cancer Research and Therapeutics 2017 13(6):936-942

Background: Compton-scattered photons transfer incorrect spatial information. These photons are detected in used photo-peak energy window. In this study, three scatter correction procedures including dual-energy window (DEW), three energy window (TEW), and new approach were evaluated, and then the best procedure based on simulation and clinical conditions introduced. Materials and Methods: In this study, simulation projections and three-dimensional nonuniform rational B-spline–based Cardiac-Torso phantoms were produced by GEANT4 application for emission tomography simulation code. For clinical study, 2-day stress/rest myocardial perfusion imaging (MPI) protocol was performed with 99m Tc-sestamibi for 46 patients. Image quality parameters including contrast, signal-to-noise ratio (SNR), and relative noise of the background (RNB) were evaluated. Results: The simulation results showed that contrast values for DEW, TEW, and new approach were (0.45 ± 0.07, 0.5 ± 0.08, and 0.63 ± 0.09), SNR values (4.74 ± 0.94, 5.58 ± 1.08, and 6.56 ± 1.24), and RNB values (0.33 ± 0.06, 0.33 ± 0.07, and 0.33 ± 0.05), respectively. In clinical study, the contrast values for DEW, TEW, and new approach were 0.53 ± 0.03, 0.57 ± 0.07, and 0.62 ± 0.04 in rest MPI and were 0.52 ± 0.04, 0.57 ± 0.06, and 0.6 ± 0.05 in stress MPI, respectively. Moreover, for the rest images, the SNR values were 7.65 ± 1.9, 9.08 ± 2.2, and 10.2 ± 1.75 and for stress images were 7.76 ± 1.99, 9.12 ± 2.25, and 10.17 ± 2.04, respectively. Finally, RNB values for rest and stress images were 0.12 ± 0.03, 0.13 ± 0.03, and 0.13 ± 0.03, respectively. Conclusion: The simulation and the clinical studies showed that the new approach could be better performance than DEW, TEW methods, according to values of the contrast, and the SNR for scatter correction.

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Detection of balanced translocations in acute lymphoblastic leukemia by a novel multiplex reverse transcriptase reverse transcription-polymerase chain reaction

Jyoti Kotwal, Madakshira Gopal Manoj, Rajan Kapoor

Journal of Cancer Research and Therapeutics 2017 13(6):1042-1046

Fusion transcripts detection is essential for subtyping and diagnosis of acute lymphoblastic leukemia (ALL). This enables institution of appropriate therapy and provides a parameter to monitor disease progression and response to therapy. This study endeared to detect and analyze various balanced translocations known in ALL by using a novel polymerase chain reaction (PCR) method. A pilot study was done in which 16 consecutive cases of ALL were analyzed and followed-up for a period of 1 year. Diagnosis of ALL was established after subjecting blood/bone marrow aspirate samples to morphological examination, immunophenotyping, and detection of fusion transcripts by multiplex reverse transcription (RT)-PCR using HemaVision kit. Results were analyzed by correlating with morphology, immunophenotype, and response to therapy. Epi-Info statistical software was used. 43% (seven cases) showed balanced translocations, with all seven cases being B-ALL and t(9;22) being the most common. There was a consistent association of CD25 cases with t(9;22). Analyses of relation to other parameters were as expected by their respective WHO 2008 subtype. No significant correlation in terms of survival benefit was seen between cases with and without balanced translocations (P = 0.7472). The study demonstrated the utility of multiplex RT-PCR in the initial evaluation, subtyping, and monitoring minimal residual disease in ALL cases with balanced translocations, thereby guiding both therapy and prognosis. The consistent association of CD25 in cases of t(9;22) ALL indicated that CD25 could be used as a surrogate marker.

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Blastic plasmacytoid dendritic cell neoplasm presenting as leukemia without cutaneous lesion

Namrata Punit Awasthi, Sumaira Qayoom, Sunil Dabadghao

Journal of Cancer Research and Therapeutics 2017 13(6):1056-1058

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy, recognized as a distinct entity in the WHO 2008 classification of hematolymphoid neoplasm. Described for the first time in 1994 as CD4+ cutaneous lymphoma with high expression of CD56, BPDCN has been known previously with various names such as blastic natural killer (NK) leukemia/lymphoma, agranular CD4+ CD56+ hematodermic neoplasm, and agranular CD4+ NK cell leukemia. This disease usually presents with cutaneous involvement as the first manifestation, with subsequent or simultaneous spread to bone marrow and peripheral blood. Leukemia as the first presenting symptom without any cutaneous involvement is a rare finding and can masquerade as acute undifferentiated leukemia. We present here such a case of a 59-year-old male who presented as leukemia without any cutaneous lesion but subsequently developed a scalp nodule.

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Utility of the laminin immunohistochemical stain in distinguishing invasive from noninvasive urothelial carcinoma

Dinesh Pradhan, Milon Amin, Shveta Hooda, Rajiv Dhir, Sheldon Bastacky, Anil V Parwani

Journal of Cancer Research and Therapeutics 2017 13(6):947-950

Background: To study the utility of the laminin immunostain in distinguishing invasive from noninvasive urothelial carcinoma (UC). The distinction is difficult but clinically significant as it can affect the decision to administer intravesical Bacillus Calmette–Guerin or can even lead to cystectomy. Materials and Methods: Representative sections of the transurethral resection of bladder tumor specimens from 25 cases of formalin-fixed paraffin-embedded invasive UCs and 25 cases of noninvasive UCs were selected for immunohistochemical (IHC) staining with laminin (Ventana, Oro Valley, AZ, USA). These cases were selected using a computer-assisted search of our laboratory information system (Cerner CoPath). Tissue from five paraffin-embedded tissue blocks containing unremarkable urothelial-lined bladder parenchyma was chosen as controls. Results: All five control cases demonstrated crisp linear staining of the basement membrane underlying the unremarkable urothelium. Similar findings were also noted in the 25 cases of noninvasive UC. All 25 cases of the invasive UC demonstrated a complete absence of the staining around invasive and malignant urothelial cells. Laminin staining was also noted in both the muscularis mucosae and the detrusor muscle, although the pattern of staining in these areas was granular and was distinguishable from the crisp linear staining of the basement membrane. Conclusion: Laminin IHC staining can be useful in differentiating invasive from noninvasive UC.

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Incision site metastasis: Adding insult to injury

Ranil Johann Boaz, Tanush Vig, Ramani Manojkumar, Antony Devasia

Journal of Cancer Research and Therapeutics 2017 13(6):1068-1069

Incision site metastasis is a rare yet well-recognized complication of oncologic operations. We describe the case of a 60-year-old man with a large mass at the site of abdominal incision for a nephrectomy. The operation was performed for infection in an obstructed kidney, which in retrospect harbored malignancy. Percutaneous core biopsy of the mass revealed metastatic conventional renal cell carcinoma (RCC). Surgical resection was obviated by the presence of nodal disease on imaging. Palliative targeted therapy with tyrosine kinase inhibitor was initiated. RCC can not only mimic an inflammatory renal mass radiologically but also coexist with infective renal conditions. Diligent histopathological examination as a routine following nephrectomy for complicated diagnoses is imperative.

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Efficacy of centrifuged liquid-based cytology over conventional cytology: A comparative study

Veda Hegde, Shwetha Nambiar, Nikhil Yadav

Journal of Cancer Research and Therapeutics 2017 13(6):951-955

Background: Exfoliative cytology is the microscopic examination of a shed or desquamated cells from the epithelial surface. Centrifuged liquid-based cytology (CLBC) is a modified technique that is used in the current study. Aims: To compare the efficacy of CLBC with conventional cytology in apparently normal mucosa and histologically proven cases of oral squamous cell carcinoma after staining with Papanicolaou stain. Materials and Methods: The study sample was collected from fifty individuals with no habits and apparently normal oral mucosa (Group 1) and forty cases of histologically proven cases of oral squamous cell carcinoma (Group 2). One smear was taken and spread on the slide by a conventional technique. The second sample was flushed out in a suspending solution, centrifuged, and the cell pellet obtained was used to make the smear. The stained smears were compared for nine parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, cellular elongation, mucus, inflammatory blood, and microbial colonies. Chi-square test was used for statistical analysis and P ≤ 0.05 was considered statistically significant. Results: There was a statistically significant result with parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, and cellular elongation in CLBC technique, in comparison with the conventional technique. The presence of mucus, microbial colonies, and inflammatory cells were also less in CLBC technique in comparison with the conventional technique. Conclusion: CLBC has better efficacy over conventional method in all the parameters analyzed.

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The effect of ciprofloxacin on the growth of B16F10 melanoma cells

Dalal Fares Jaber, Mary-Ann Nabil Jallad, Alexander Micheal Abdelnoor

Journal of Cancer Research and Therapeutics 2017 13(6):956-960

Objective: The antitumor effect of ciprofloxacin has been widely assessed in-vitro, and positive results have been reported. The aim of this study was to investigate the influence of ciprofloxacin treatment on the growth of B16F10 melanoma cells both in-vitro and in-vivo. Materials and Methods: Groups of C57BL/6 female mice challenged with B16F10 melanoma cells were kept untreated or were treated with sterile water, intraperitoneal ciprofloxacin, or ciprofloxacin through drinking water for 10 days. The serum levels of vascular endothelial growth factor (VEGF) were measured by ELISA 1 and 3 h after the last dose of ciprofloxacin. Mice were monitored for an additional 10 days for survival assessment. Moreover, B16F10 melanoma cells were cultured in 24-well plates and exposed to different concentrations of ciprofloxacin (10–1000 μg/ml). Viability was determined, after 24 and 48 h, using trypan blue. Results: The serum levels of VEGF significantly decreased in ciprofloxacin-treated mice when compared to the controls. None of the control mice survived beyond day 8, whereas 16.67% of those treated with ciprofloxacin survived up to 18 days. In addition, the viability of B16F10 melanoma cells, in-vitro, significantly decreased with increasing concentrations of ciprofloxacin after 24 and 48 h. Conclusion: Ciprofloxacin seems to exhibit antitumor activity both in-vivo and in-vitro. This effect might be explained by several mechanisms such as directly inducing cancer cell death or altering the immune response through the modification of the normal microbiota.

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Choroidal metastases as the presenting feature of adenocarcinoma of the lung: A case report and an overview of the role of radiotherapy in its management

Krishna Sharan, S Shailaja, Vijaya H Pai, Donald J Fernandes

Journal of Cancer Research and Therapeutics 2017 13(6):1062-1064

Although metastasis to the eye is the most common ophthalmic malignancy, it is usually asymptomatic and rarely a presenting symptom that leads to the diagnosis of a primary. Here, we report a patient who was evaluated for visual symptoms and was eventually diagnosed to have disseminated adenocarcinoma of the lung. He was treated with external radiotherapy to the choroidal metastasis, attaining an excellent response that was sustained until his death. A brief review on the role of radiotherapy in the management of uveal metastases is also presented.

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Diagnosis and management of gastrointestinal stromal tumors: An up-to-date literature review

Ayman El-Menyar, Ahammed Mekkodathil, Hassan Al-Thani

Journal of Cancer Research and Therapeutics 2017 13(6):889-900

Gastrointestinal stromal tumors (GISTs) are rare life-threatening forms of cancer that may arise anywhere in the GI tract. Herein, we aimed to review the literature to describe the incidence, management, and outcomes of GISTs. We conducted a traditional narrative review using PubMed and EMBASE, searching for English-language publications for GISTs between January 2001 and January 2016 using keywords ""gastrointestinal" "stromal tumors." Among 4582 retrieved articles, 50 articles were relevant over the last 15 years. Several risk stratification systems exist to predict the outcomes of GISTs based on certain criteria such as the primary site of occurrence, size of the tumor, mitotic activity, staining for proliferating cells, and tumor necrosis. Risk stratification is crucial in the management and outcomes of the disease. Surgical resection remains the gold standard option of GISTs treatment. Complete resection of the tumor is the main predictor of the postoperative patient's survival. Laparoscopic resections are associated with less intraoperative blood loss, early return of bowel function, early resumption of diet, and short hospital stay. However, laparoscopy is difficult to perform in large and unfavorably placed GISTs and may result in disease progression, recurrence, and poor survival. Robot-assisted laparoscopic resections provide instruments for surgeons to perform technically demanding operations. Moreover, extensive research work including large clinical trials is ongoing to establish promising role of the adjuvant and neo-adjuvant therapy for better disease- free survival in GIST patients.

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Expression of WW domain-containing protein 2 is correlated with pathological grade and recurrence of glioma

Jun Liang, Wei-Feng Qi, Shao Xie, Wei-Feng Wang, Xian-Li Zhang, Xiu-Ping Zhou, Qiong-Shi , Jin-Xia Hu, Ru-Tong Yu

Journal of Cancer Research and Therapeutics 2017 13(6):1032-1037

Objective: WW domain-containing protein 2 (WWP2) is an E3 ubiquitin ligase, which belongs to the NEDD4-like protein family. Recently, it is reported to play a key role in tumorigenesis and development of tumors such as prostate and lung cancer. However, there has been not related report on glioma until now. The aim of this study is to detect the expression of WWP2 and analyze its correlation to the pathological grade and tumor recurrence in patients with glioma. Materials and Methods: Western blot and immunohistochemistry were separately used to detect the expression of WWP2 protein in 31 brain glioma tissue samples and 80 brain glioma paraffin specimens. The method of Kaplan–Meier was used to analyze the correlation between the WWP2 expression and glioma recurrence. Results: The protein expression level of WWP2 in glioma tissue was significantly higher than that in nontumorous brain tissue (P < 0.05), and the protein expression level of WWP2 in high-grade glioma (Grade III–IV) was significantly higher than that in low-grade glioma (Grade I–II) (P < 0.05). Kaplan–Meier analysis indicated that the patients with high WWP2 expression had significantly shorter tumor recurrence time than the patients with low WWP2 expression (P < 0.05). Conclusion: Our study suggests that WWP2 may play a role in the genesis and development of glioma; it may be a potential biomarker to predict pathological grade and tumor recurrence in patients with glioma.

http://ift.tt/2o252kL

Extramedullary sarcomatoid variant of plasmablastic plasmacytoma

Urmila Majhi, Shirley Sundersingh, Kanchan Murhekar, Krishnamurthy Radha

Journal of Cancer Research and Therapeutics 2017 13(6):1078-1079



http://ift.tt/2nXNXs8

Optical diagnostics in oral cancer: An update on Raman spectroscopic applications

Aditi Sahu, C Murali Krishna

Journal of Cancer Research and Therapeutics 2017 13(6):908-915

Raman spectroscopy (RS) is a sensitive vibrational spectroscopic method that can detect even subtle biochemical changes during the onset of disease. Consequently, RS has been extensively investigated for disease diagnosis, including cancers. Oral cancers are known to suffer from dismal survival rates, which have not improved for several decades. As delayed diagnosis contributes to the low disease-free survival rate observed in oral cancers, RS has also been explored for the early diagnosis of oral cancers. This review summarizes the major developments in the field, including diagnosis, surgical margin assessment and prediction of treatment response, and in the overall management of oral cancers. The article comprises an overview of epidemiology, diagnosis, treatment, and recently introduced diagnostic adjuncts for oral cancers, the basic principle, instrumentation of RS, multivariate analysis that impart objectivity to the approach, and finally a discussion on the recent applications in oral cancers. PubMed and Google Scholar database have been used to compile information available online till December 2015.

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Intrarectal fixative for positioning of the prostate for intensity modulated radiotherapy

Janos Stumpf, Subathira Balasundaram, P. G. G. Kurup, Rathnadevi Ramadas, Murali Venkatraman, Karthikeyan Perumal

Journal of Cancer Research and Therapeutics 2017 13(6):1050-1052

Dose escalation improves local control in carcinoma prostate, but rectal toxicity remains a concern. Various techniques have been there to reduce the dose to the rectum. Mobility of the prostate results in a necessary expansion of the target volume. We describe a new intrarectal fixative, developed in-house with transrectal ultrasonography through the fixative itself for localization of the organ by reporting a case with early carcinoma prostate. Concerns of rectal toxicity limit dose escalation in the treatment of prostate cancer. Intra- and interfraction prostate motion is a concern in dose conformity techniques. The intrarectal fixative system developed in-house physically separates the prostate and rectum during radiation treatment. Thus, both intra- and inter-fractional movement of the organ are addressed, therefore planning target volume expansion can be kept minimal.

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Cancer-related fatigue treatment: An overview

Hemanth Mohandas, Saravana Kumar Jaganathan, Mohan Prasath Mani, Manikandan Ayyar, GV Rohini Thevi

Journal of Cancer Research and Therapeutics 2017 13(6):916-929

Cancer-related fatigue is a symptom of cancer where most patients or the general practitioners tend to misinterpret due to the insufficient understanding or knowledge of cancer-related fatigue (CRF). This paper will provide a better perspective for the patients and the health professionals on how to manage and handle CRF for both mild and severe fatigue patients. Articles were selected from the searches of PubMed database that had the terms "randomized controlled trials," "cancer," "fatigue," "pharmacologic treatment," and "nonpharmacologic treatment" using both Mesh terms and keywords. The authors have reviewed the current hypothesis and evidence of the detailed etiology of the CRF present in the literature for healthier management, directives, and strategies to improve the treatment of cancer-related fatigue. An algorithm has been blueprinted on screening, and management, of the CRF, and various kinds of effective treatments and assessment tools have been briefly studied and explained. Although many strategies seemed promising, the quality of randomized controlled trials is generally quite low in studies, making it difficult to draw conclusions about the effectiveness of each self-care strategies. Therefore, future studies require better design and reporting of methodological issues to ensure evidence-based self-care recommendations for people receiving cancer treatment.

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Quantitative determination of tumor platinum concentration of patients with advanced Breast, lung, prostate, or colorectal cancers undergone platinum-based chemotherapy

Hesameddin Mostaghimi, Ali Reza Mehdizadeh, Mohammad Jahanbakhsh, Amir Reza Dehghanian, Ramin Askari

Journal of Cancer Research and Therapeutics 2017 13(6):930-935

Context: Previous studies have reported direct relationship between tumor reduction and its platinum concentration following platinum-based (Pt-based) chemotherapy. However, quantitative data of tumor platinum concentration have not yet been reported for the most common cancers. Aims: Determination of tumor platinum concentration of breast, lung, prostate, and colorectal cancers after Pt-based chemotherapy; and evaluation of the influence of chemo drug type, chemotherapy regimen, and time lapse from last chemotherapy on tumor platinum concentration. Materials and Methods: Tumor samples of patients with advanced breast, lung, prostate, and colorectal cancers undergone Pt-based chemotherapy were collected from pathology collection of various hospitals. The platinum concentration of each sample was measured by inductively coupled plasma optical emission spectrometry. The data were categorized by drug type, time lapse from last chemotherapy, and regimen type to evaluate their effects on platinum concentration. Statistical Analysis: ANOVA, Mann–Whitney U and Kruskal–Wallis tests were used. Results: Tumor platinum concentrations of breast, lung, prostate, and colorectal cancers were all obtained in the range of 1–10 μg/g tumor tissue. Large values of P (>0.05) indicate no significant differences between various chemo drug, regimen, and time groups. Conclusions: In general, the platinum concentration was higher in prostate and lower in lung tumors. The type of Pt-based chemo drug, time lapse from the last chemotherapy, and concurrency of other antineoplastic agents administered with Pt-based chemo drugs had no significant effect on tumor platinum concentration.

http://ift.tt/2Cdd8Ku

Agreement analysis between three different short geriatric screening scales in patients undergoing chemotherapy for solid tumors

Amit Joshi, Nidhi Tandon, Vijay M Patil, Vanita Noronha, Sudeep Gupta, Atanu Bhattacharjee, Kumar Prabhash

Journal of Cancer Research and Therapeutics 2017 13(6):1023-1026

Background: Comprehensive geriatric assessment (CGA) in routine practice is not logistically feasible. Short geriatric screening tools are available for selecting patients for CGA. However none of them is validated in India. In this analysis we aim to compare the level of agreement between three commonly used short screening tools (Flemish version of TRST (fTRST), G8 and VES-13. Methods: Patients ≥65 years with a solid tumor malignancy undergoing cancer directed treatment were interviewed between March 2013 to July 2014. Geriatric screening with G8, fTRST and VES-13 tools was performed in these patients. G8 score ≤14, fTRST score ≥1 and VES-13 score ≥3 were taken as indicators for the presence of a high risk geriatric profile respectively. R version 3.1.2 was used for analysis. Cohen kappa agreement statistics was used to compare the agreement between the 3 tools. p value of 0.05 was taken as significant. Results: The kappa statistics value for agreement between G8 score and fTRST, between VES-13 and fTRST and between VES-13 and G8 were 0.12 (P = 0.04), 0.16 (P = 0.07) and 0.05 (P = 0.45) respectively. It was found that maximum agreement was observed for VES-13 and fTRST. The agreement value of VES-13 and fTRST observed was 59.44 %(39.63% for high risk profile and 19.81% for low risk profile). The agreement value of G-8 and fTRST was 39.62% (2.83% only for high risk profile and 36.79% for low risk profile). The lowest agreement was between G8 and VES-13, 35.84% (7.54% for high risk detection and 28.30% for low risk detection). Conclusion: There was poor agreement (in view of kappa value been below 0.2) between the 3 short geriatric screening tools. Research needs to be directed to compare the agreement level between these 3 scales and CGA, so that the appropriate short screening tool can be selected for routine use.

http://ift.tt/2nZSRVH

Assessment of the scatter correction procedures in single photon emission computed tomography imaging using simulation and clinical study

Mehravar Rafati, Hemmatollah Rouhani, Ahmad Bitarafan-Rajabi, Mahsa Noori-Asl, Bagher Farhood, Hadi Taleshi Ahangari

Journal of Cancer Research and Therapeutics 2017 13(6):936-942

Background: Compton-scattered photons transfer incorrect spatial information. These photons are detected in used photo-peak energy window. In this study, three scatter correction procedures including dual-energy window (DEW), three energy window (TEW), and new approach were evaluated, and then the best procedure based on simulation and clinical conditions introduced. Materials and Methods: In this study, simulation projections and three-dimensional nonuniform rational B-spline–based Cardiac-Torso phantoms were produced by GEANT4 application for emission tomography simulation code. For clinical study, 2-day stress/rest myocardial perfusion imaging (MPI) protocol was performed with 99m Tc-sestamibi for 46 patients. Image quality parameters including contrast, signal-to-noise ratio (SNR), and relative noise of the background (RNB) were evaluated. Results: The simulation results showed that contrast values for DEW, TEW, and new approach were (0.45 ± 0.07, 0.5 ± 0.08, and 0.63 ± 0.09), SNR values (4.74 ± 0.94, 5.58 ± 1.08, and 6.56 ± 1.24), and RNB values (0.33 ± 0.06, 0.33 ± 0.07, and 0.33 ± 0.05), respectively. In clinical study, the contrast values for DEW, TEW, and new approach were 0.53 ± 0.03, 0.57 ± 0.07, and 0.62 ± 0.04 in rest MPI and were 0.52 ± 0.04, 0.57 ± 0.06, and 0.6 ± 0.05 in stress MPI, respectively. Moreover, for the rest images, the SNR values were 7.65 ± 1.9, 9.08 ± 2.2, and 10.2 ± 1.75 and for stress images were 7.76 ± 1.99, 9.12 ± 2.25, and 10.17 ± 2.04, respectively. Finally, RNB values for rest and stress images were 0.12 ± 0.03, 0.13 ± 0.03, and 0.13 ± 0.03, respectively. Conclusion: The simulation and the clinical studies showed that the new approach could be better performance than DEW, TEW methods, according to values of the contrast, and the SNR for scatter correction.

http://ift.tt/2ChLlc3

Detection of balanced translocations in acute lymphoblastic leukemia by a novel multiplex reverse transcriptase reverse transcription-polymerase chain reaction

Jyoti Kotwal, Madakshira Gopal Manoj, Rajan Kapoor

Journal of Cancer Research and Therapeutics 2017 13(6):1042-1046

Fusion transcripts detection is essential for subtyping and diagnosis of acute lymphoblastic leukemia (ALL). This enables institution of appropriate therapy and provides a parameter to monitor disease progression and response to therapy. This study endeared to detect and analyze various balanced translocations known in ALL by using a novel polymerase chain reaction (PCR) method. A pilot study was done in which 16 consecutive cases of ALL were analyzed and followed-up for a period of 1 year. Diagnosis of ALL was established after subjecting blood/bone marrow aspirate samples to morphological examination, immunophenotyping, and detection of fusion transcripts by multiplex reverse transcription (RT)-PCR using HemaVision kit. Results were analyzed by correlating with morphology, immunophenotype, and response to therapy. Epi-Info statistical software was used. 43% (seven cases) showed balanced translocations, with all seven cases being B-ALL and t(9;22) being the most common. There was a consistent association of CD25 cases with t(9;22). Analyses of relation to other parameters were as expected by their respective WHO 2008 subtype. No significant correlation in terms of survival benefit was seen between cases with and without balanced translocations (P = 0.7472). The study demonstrated the utility of multiplex RT-PCR in the initial evaluation, subtyping, and monitoring minimal residual disease in ALL cases with balanced translocations, thereby guiding both therapy and prognosis. The consistent association of CD25 in cases of t(9;22) ALL indicated that CD25 could be used as a surrogate marker.

http://ift.tt/2o3tIcE

Accelerated hypofractionation (OCTA SHOT): Palliative radiation schedule in advanced head and neck carcinoma

Shankar Lal Jakhar, Ramesh Purohit, Akankhsha Solanki, P Murali, Trupti Kothari, Neeti Sharma, Harvinder Singh Kumar

Journal of Cancer Research and Therapeutics 2017 13(6):943-946

Background: Head and neck cancers are attributed to be the most common type of malignancy in the developing countries with most cases presenting in advanced stage. This pilot study was performed to evaluate the effect of an accelerated hypofractionated 4 days schedule (octa shot) in providing palliation to such advanced cases of head and neck cancer. Materials and Methods: Twenty-two patients with advanced (Stage VIB-IVB) squamous cell carcinoma of head and neck region were enrolled in the study. All these patients were planned for radiotherapy at Cobalt Unit with a fractionation schedule of 3.5 Gy/fraction, 2 fractions/day with 6 h interval between two fractions, for four days (28 Gy/8Fr/4 days). Patients were reviewed at 2 and 4 weeks to assess change in tumor size, any symptomatic relief, or toxicity. The tumor response, dermal, and mucosal toxicities were assessed using WHO criteria. Results: Median age of these 22 patients (17M male + 5F female) in the study was 59.8 years. After completion of radiotherapy, first response evaluation done at 15th day showed ≥50% objective response in 14 patients. At 1 month, this response increased to ≥75% in 16 patients and 50%–75% in three patients. None of the patients had disease progression. Improvement in symptoms was reported with respect to pain and dysphagia by patients subjectively. Only two patients reported Grade III mucositis; remaining patients had mucositis and dermatitis up to Grade II. Conclusion: The study concludes that this "octa shot" is an effective palliative radiotherapy schedule. With a decreased duration of hospital stay, it is also favorable for outpatients.

http://ift.tt/2CeCM1r

Blastic plasmacytoid dendritic cell neoplasm presenting as leukemia without cutaneous lesion

Namrata Punit Awasthi, Sumaira Qayoom, Sunil Dabadghao

Journal of Cancer Research and Therapeutics 2017 13(6):1056-1058

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy, recognized as a distinct entity in the WHO 2008 classification of hematolymphoid neoplasm. Described for the first time in 1994 as CD4+ cutaneous lymphoma with high expression of CD56, BPDCN has been known previously with various names such as blastic natural killer (NK) leukemia/lymphoma, agranular CD4+ CD56+ hematodermic neoplasm, and agranular CD4+ NK cell leukemia. This disease usually presents with cutaneous involvement as the first manifestation, with subsequent or simultaneous spread to bone marrow and peripheral blood. Leukemia as the first presenting symptom without any cutaneous involvement is a rare finding and can masquerade as acute undifferentiated leukemia. We present here such a case of a 59-year-old male who presented as leukemia without any cutaneous lesion but subsequently developed a scalp nodule.

http://ift.tt/2o0QMca

Utility of the laminin immunohistochemical stain in distinguishing invasive from noninvasive urothelial carcinoma

Dinesh Pradhan, Milon Amin, Shveta Hooda, Rajiv Dhir, Sheldon Bastacky, Anil V Parwani

Journal of Cancer Research and Therapeutics 2017 13(6):947-950

Background: To study the utility of the laminin immunostain in distinguishing invasive from noninvasive urothelial carcinoma (UC). The distinction is difficult but clinically significant as it can affect the decision to administer intravesical Bacillus Calmette–Guerin or can even lead to cystectomy. Materials and Methods: Representative sections of the transurethral resection of bladder tumor specimens from 25 cases of formalin-fixed paraffin-embedded invasive UCs and 25 cases of noninvasive UCs were selected for immunohistochemical (IHC) staining with laminin (Ventana, Oro Valley, AZ, USA). These cases were selected using a computer-assisted search of our laboratory information system (Cerner CoPath). Tissue from five paraffin-embedded tissue blocks containing unremarkable urothelial-lined bladder parenchyma was chosen as controls. Results: All five control cases demonstrated crisp linear staining of the basement membrane underlying the unremarkable urothelium. Similar findings were also noted in the 25 cases of noninvasive UC. All 25 cases of the invasive UC demonstrated a complete absence of the staining around invasive and malignant urothelial cells. Laminin staining was also noted in both the muscularis mucosae and the detrusor muscle, although the pattern of staining in these areas was granular and was distinguishable from the crisp linear staining of the basement membrane. Conclusion: Laminin IHC staining can be useful in differentiating invasive from noninvasive UC.

http://ift.tt/2CeCLdT

Incision site metastasis: Adding insult to injury

Ranil Johann Boaz, Tanush Vig, Ramani Manojkumar, Antony Devasia

Journal of Cancer Research and Therapeutics 2017 13(6):1068-1069

Incision site metastasis is a rare yet well-recognized complication of oncologic operations. We describe the case of a 60-year-old man with a large mass at the site of abdominal incision for a nephrectomy. The operation was performed for infection in an obstructed kidney, which in retrospect harbored malignancy. Percutaneous core biopsy of the mass revealed metastatic conventional renal cell carcinoma (RCC). Surgical resection was obviated by the presence of nodal disease on imaging. Palliative targeted therapy with tyrosine kinase inhibitor was initiated. RCC can not only mimic an inflammatory renal mass radiologically but also coexist with infective renal conditions. Diligent histopathological examination as a routine following nephrectomy for complicated diagnoses is imperative.

http://ift.tt/2o3tF0s

Efficacy of centrifuged liquid-based cytology over conventional cytology: A comparative study

Veda Hegde, Shwetha Nambiar, Nikhil Yadav

Journal of Cancer Research and Therapeutics 2017 13(6):951-955

Background: Exfoliative cytology is the microscopic examination of a shed or desquamated cells from the epithelial surface. Centrifuged liquid-based cytology (CLBC) is a modified technique that is used in the current study. Aims: To compare the efficacy of CLBC with conventional cytology in apparently normal mucosa and histologically proven cases of oral squamous cell carcinoma after staining with Papanicolaou stain. Materials and Methods: The study sample was collected from fifty individuals with no habits and apparently normal oral mucosa (Group 1) and forty cases of histologically proven cases of oral squamous cell carcinoma (Group 2). One smear was taken and spread on the slide by a conventional technique. The second sample was flushed out in a suspending solution, centrifuged, and the cell pellet obtained was used to make the smear. The stained smears were compared for nine parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, cellular elongation, mucus, inflammatory blood, and microbial colonies. Chi-square test was used for statistical analysis and P ≤ 0.05 was considered statistically significant. Results: There was a statistically significant result with parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, and cellular elongation in CLBC technique, in comparison with the conventional technique. The presence of mucus, microbial colonies, and inflammatory cells were also less in CLBC technique in comparison with the conventional technique. Conclusion: CLBC has better efficacy over conventional method in all the parameters analyzed.

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The feasibility of smoker's surcharge policy in tobacco control

Eby Aluckal, Sanju Lakshmanan

Journal of Cancer Research and Therapeutics 2017 13(6):1075-1076



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The effect of ciprofloxacin on the growth of B16F10 melanoma cells

Dalal Fares Jaber, Mary-Ann Nabil Jallad, Alexander Micheal Abdelnoor

Journal of Cancer Research and Therapeutics 2017 13(6):956-960

Objective: The antitumor effect of ciprofloxacin has been widely assessed in-vitro, and positive results have been reported. The aim of this study was to investigate the influence of ciprofloxacin treatment on the growth of B16F10 melanoma cells both in-vitro and in-vivo. Materials and Methods: Groups of C57BL/6 female mice challenged with B16F10 melanoma cells were kept untreated or were treated with sterile water, intraperitoneal ciprofloxacin, or ciprofloxacin through drinking water for 10 days. The serum levels of vascular endothelial growth factor (VEGF) were measured by ELISA 1 and 3 h after the last dose of ciprofloxacin. Mice were monitored for an additional 10 days for survival assessment. Moreover, B16F10 melanoma cells were cultured in 24-well plates and exposed to different concentrations of ciprofloxacin (10–1000 μg/ml). Viability was determined, after 24 and 48 h, using trypan blue. Results: The serum levels of VEGF significantly decreased in ciprofloxacin-treated mice when compared to the controls. None of the control mice survived beyond day 8, whereas 16.67% of those treated with ciprofloxacin survived up to 18 days. In addition, the viability of B16F10 melanoma cells, in-vitro, significantly decreased with increasing concentrations of ciprofloxacin after 24 and 48 h. Conclusion: Ciprofloxacin seems to exhibit antitumor activity both in-vivo and in-vitro. This effect might be explained by several mechanisms such as directly inducing cancer cell death or altering the immune response through the modification of the normal microbiota.

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Cadmium Testicular Toxicity in Male Wistar Rats: Protective Roles of Zinc and Magnesium

Abstract

Cadmium (Cd) is a highly toxic element, which may cause toxicity to most organs in the body. Zinc (Zn) and magnesium (Mg) are essential minerals with probable benefits on Cd harmful effects. Finding an efficient and non-pathological treatment against Cd toxicity seems promising. Fifty adult rats were divided into ten experimental groups of five rats each. The Cd group was treated with 1 mg Cd/kg and the control group received 0.5 cm³ normal saline. The other eight groups received Zn (0.5 and 1.5 mg/kg) and Mg (0.5 and 1.5 mg/kg) either alone or in combination with 1 mg Cd/kg through IP injection for 3 weeks. Testis malondialdehyde (MDA), sperm parameters, and testis histopathology were investigated. Cd reduced sperm parameters and increased testis MDA. Moreover, Cd exposure caused a significant histological damage in testis of male rats. However, Zn or Mg treatment prevented and reversed Cd toxic alterations in testis. These findings suggest that co-administration of Zn or Mg could improve cadmium testicular toxicity in male Wistar rats.

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Cadmium Testicular Toxicity in Male Wistar Rats: Protective Roles of Zinc and Magnesium

Abstract

Cadmium (Cd) is a highly toxic element, which may cause toxicity to most organs in the body. Zinc (Zn) and magnesium (Mg) are essential minerals with probable benefits on Cd harmful effects. Finding an efficient and non-pathological treatment against Cd toxicity seems promising. Fifty adult rats were divided into ten experimental groups of five rats each. The Cd group was treated with 1 mg Cd/kg and the control group received 0.5 cm³ normal saline. The other eight groups received Zn (0.5 and 1.5 mg/kg) and Mg (0.5 and 1.5 mg/kg) either alone or in combination with 1 mg Cd/kg through IP injection for 3 weeks. Testis malondialdehyde (MDA), sperm parameters, and testis histopathology were investigated. Cd reduced sperm parameters and increased testis MDA. Moreover, Cd exposure caused a significant histological damage in testis of male rats. However, Zn or Mg treatment prevented and reversed Cd toxic alterations in testis. These findings suggest that co-administration of Zn or Mg could improve cadmium testicular toxicity in male Wistar rats.

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Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT).

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Local recurrences after curative IMRT for HNSCC: Effect of different GTV to high-dose CTV margins

The aim was to analyze position of CT-verified local recurrences (LR) and local control (LC) among three centers that used different GTV to CTV1 margins.

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Current Treatments for Surgically Resectable, Limited‐Stage, and Extensive‐Stage Small Cell Lung Cancer

AbstractThe prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor‐1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra‐thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited‐stage disease, concurrent platinum‐etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60–70 Gy. For extensive‐stage disease, platinum‐etoposide remains the standard first‐line therapy, and the standard second‐line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10–30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta‐like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first‐line, maintenance, and second‐line settings.Implications for Practice.This review will provide an update on the standard therapies for surgically resected limited‐stage small cell lung cancer and extensive‐stage small cell lung cancer that have been investigated in recent clinical trials.

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Early Integrated Palliative Care and Reduced Emotional Distress in Cancer Caregivers: Reaching the “Hidden Patients”

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In Reply

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Development of Molecularly Driven Targeted Combination Strategies

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In Reply

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Clinical Trials in Pancreatic Cancer: A Long Slog

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Feasibility and Efficacy of Microwave Ablation Combined with Iodine‐125 Seed Implantation in Local Control of Recurrent Retroperitoneal Liposarcomas: Initial Clinical Experience

AbstractIntroduction.The objective of the present study was to evaluate the feasibility, safety, and short‐term efficacy of microwave ablation (MWA) combined with iodine‐125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs).Materials and Methods.From September 2012 to March 2015, 11 patients were enrolled in this prospective study. Eleven tumors (median, 9 cm; range, 5.5–12.5 cm) were treated with computerized tomography‐guided MWA for 11 sessions and 125I seed implantation for 18 sessions. 125I seed implantation was performed 4 weeks after MWA.Results.There were no procedure‐related deaths. Post‐MWA pain (grade ≥2) was the most common complication (6 of 11 patients, 54.5%), and fever (grade ≥2) was observed in two patients. Reversible nerve injury, defined as transient limb paresthesia or leg weakness, was observed in one patient. There were fewer complications associated with the 125I seed implantation procedure compared with the MWA procedure. All 11 patients who underwent the MWA procedure achieved a partial response (PR), according to the modified Response Evaluation Criteria in Solid Tumors, 1 month post‐ablation; after 125I seed implantation was performed, a complete response was observed in three, five, and six target tumors in 3, 6, and 12 months, respectively.Conclusion.In selected patients with rRPLs, MWA combined with 125I seed implantation is feasible and safe with favorable local control efficacy.Implications for Practice.This study evaluated the feasibility, safety, and short‐term efficacy of microwave ablation (MWA) combined with iodine‐125 (125I) seed implantation in recurrent retroperitoneal liposarcomas (rRPLs). Results suggest that a single session of MWA may be not sufficient in large‐volume rRPLs and that as a supplement treatment, 125I seed implantation is safe and easy accessible. MWA combined with 125I seed has excellent local control effectiveness, and long‐term efficacy and survival benefit still need to be more comprehensively evaluated.

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A Randomized, Double‐Blinded, Phase II Trial of Gemcitabine and Nab‐Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial

AbstractLessons Learned. The addition of the heat shock protein 27 (Hsp27)‐targeting antisense oligonucleotide, apatorsen, to a standard first‐line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation.Background.This randomized, double‐blinded, phase II trial evaluated the efficacy of gemcitabine/nab‐paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer.Methods.Patients were randomized 1:1 to Arm A (gemcitabine/nab‐paclitaxel plus apatorsen) or Arm B (gemcitabine/nab‐paclitaxel plus placebo). Treatment was administered in 28‐day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS).Results.One hundred thirty‐two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment‐related adverse events for both arms. Median progression‐free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor‐prognosis subgroup who may have derived modest benefit from addition of apatorsen.Conclusion.Addition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first‐line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup.

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Effects of Early Integrated Palliative Care on Caregivers of Patients with Lung and Gastrointestinal Cancer: A Randomized Clinical Trial

AbstractBackground.The family and friends (caregivers) of patients with advanced cancer often experience tremendous distress. Although early integrated palliative care (PC) has been shown to improve patient‐reported quality of life (QOL) and mood, its effects on caregivers' outcomes is currently unknown.Materials and Methods.We conducted a randomized trial of early PC integrated with oncology care versus oncology care alone for patients who were newly diagnosed with incurable lung and noncolorectal gastrointestinal cancers and their caregivers. The early PC intervention focused on addressing the needs of both patients and their caregivers. Eligible caregivers were family or friends who would likely accompany patients to clinic visits. The intervention entailed at least monthly patient visits with PC from the time of diagnosis. Caregivers were encouraged, but not required, to attend the palliative care visits. We used the Hospital Anxiety and Depression Scale (HADS) and Medical Health Outcomes Survey Short‐Form to assess caregiver mood and QOL.Results.Two hundred seventy‐five caregivers (intervention n = 137; control n = 138) of the 350 patients participated. The intervention led to improvement in caregivers' total distress (HADS‐total adjusted mean difference = −1.45, 95% confidence interval [CI] −2.76 to −0.15, p = .029), depression subscale (HADS‐depression adjusted mean difference = −0.71, 95% CI −1.38 to −0.05, p = .036), but not anxiety subscale or QOL at week 12. There were no differences in caregivers' outcomes at week 24. A terminal decline analysis showed significant intervention effects on caregivers' total distress (HADS‐total), with effects on both the anxiety and depression subscales at 3 and 6 months before patient death.Conclusion.Early involvement of PC for patients with newly diagnosed lung and gastrointestinal cancers leads to improvement in caregivers' psychological symptoms. This work demonstrates that the benefits of early, integrated PC models in oncology care extend beyond patient outcomes and positively impact the experience of caregivers.Implications for Practice.Early involvement of palliative care for patients with newly diagnosed lung and gastrointestinal cancers leads to improvement in caregivers' psychological symptoms. The findings of this trial demonstrate that the benefits of the early, integrated palliative care model in oncology care extend beyond patient outcomes and positively impact the experience of caregivers. These findings contribute novel data to the growing evidence base supporting the benefits of integrating palliative care earlier in the course of disease for patients with advanced cancer and their caregivers.

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Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Necuparanib Combined with Nab‐Paclitaxel and Gemcitabine in Patients with Metastatic Pancreatic Cancer: Phase I Results

AbstractLessons Learned. Despite the compelling preclinical rationale of evaluating the genetically engineered heparin derivative, necuparanib, combined with standard therapy in metastatic pancreas adenocarcinoma, the results were ultimately disappointing.Safety was documented, although dose escalation was limited by the number of subcutaneous injections, the potential for skin toxicity (cellulitis), and low‐level anticoagulant effect. Nonetheless, the hypothesis of targeting prothrombotic pathways in pancreas adenocarcinoma remains compelling.Background.Necuparanib is derived from unfractionated heparin and engineered for reduced anticoagulant activity while preserving known heparin‐associated antitumor properties. This trial assessed the safety, pharmacokinetics (PK), pharmacodynamics, and initial efficacy of necuparanib combined with gemcitabine ± nab‐paclitaxel in patients with metastatic pancreatic cancer.Methods.Patients received escalating daily subcutaneous doses of necuparanib plus 1,000 mg/m2 gemcitabine (days 1, 8, 15, and every 28 days). The protocol was amended to include 125 mg/m2 nab‐paclitaxel after two cohorts (following release of the phase III MPACT data). The necuparanib starting dose was 0.5 mg/kg, with escalation via a modified 3 + 3 design until the maximum tolerated dose (MTD) was determined.Results.Thirty‐nine patients were enrolled into seven cohorts (necuparanib 0.5, 1 mg/kg + gemcitabine; necuparanib 1, 2, 4, 6, and 5 mg/kg + nab‐paclitaxel + gemcitabine). The most common adverse events were anemia (56%), fatigue (51%), neutropenia (51%), leukopenia (41%), and thrombocytopenia (41%). No deaths and two serious adverse events were potentially related to necuparanib. Measurable levels of necuparanib were seen starting at the 2 mg/kg dose. Of 24 patients who received at least one dose of necuparanib + nab‐paclitaxel + gemcitabine, 9 (38%) achieved a partial response and 6 (25%) achieved stable disease (63% disease control rate). Given a cellulitis event and mild activated partial thromboplastin time increases at 6 mg/kg, the 5 mg/kg dose was considered the MTD and selected for further assessment in phase II.Conclusion.Acceptable safety and encouraging signals of activity in patients with metastatic pancreatic cancer receiving necuparanib, nab‐paclitaxel, and gemcitabine were demonstrated.

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Volume 22 Acknowledgments

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Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case‐Control Study in Northern and Eastern China and Implications for Chemoprevention

AbstractBackground.Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear.Materials and Methods.We conducted a case‐control study including 1,439 breast cancer cases in Northern and Eastern China. Both ER and progesterone receptor (PR) statuses were available for 1,316 cases. Associations between body size‐related factors and breast cancer risk defined by receptor status were assessed by multiple polytomous unconditional logistic regression analysis.Results.Body mass index and WHR were positively associated with overall breast cancer risk. Body mass index was positively associated with both ER+/PR positive (PR+) and ER negative (ER−)/PR negative(PR−) subtype risks, although only significantly for ER+/PR+ subtype. Waist–hip ratio was only positively correlated with ER−/PR− subtype risk, although independent of BMI. Body mass index was positively associated with risk of ER+/PR+ and ER−/PR− subtypes in premenopausal women, whereas WHR was inversely correlated with ER+/PR− and positively with ER−/PR− subtype risks. Among postmenopausal women, WHR >0.85 was associated with increased risk of ER−/PR− subtype.Conclusion.Both general and central obesity contribute to breast cancer risk, with different effects on specific subtypes. General obesity, indicated by BMI, is more strongly associated with ER+/PR+ subtype, especially among premenopausal women, whereas central obesity, indicated by WHR, is more specific for ER−/PR− subtype, independent of menopausal status. These results suggest that different chemoprevention strategies may be appropriate in selected individuals.Implications for Practice.The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes, supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens. The results also imply that different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor negative breast cancer, stricter weight‐control measures may be advised in these individuals.

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The Search for Surrogate Endpoints in Trials in Diffuse Large B‐Cell Lymphoma: The Surrogate Endpoints for Aggressive Lymphoma Project

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ALK Fusions in a Wide Variety of Tumor Types Respond to Anti‐ALK Targeted Therapy

AbstractBackground.Genomic fusions of the anaplastic lymphoma kinase gene (ALK) are a well‐established therapy target in non‐small cell lung cancer (NSCLC). From a survey of 114,200 clinical cases, we determined the prevalence of ALK rearrangements (rALK) in non‐NSCLC tumors and report their responsiveness to therapies targeting ALK.Materials and Methods.Comprehensive genomic profiling of 114,200 relapsed and metastatic malignancies, including both solid tumors and hematolymphoid cancers, was performed using a hybrid‐capture, adaptor ligation‐based next‐generation sequencing assay.Results.Of 114,200 clinical samples, 21,522 (18.8%) were NSCLC and 92,678 (81.2%) were other tumor types. Of the 876 (0.8%) cases with ALK fusions (fALK) or rALK, 675 (77.1%) were NSCLC and 201 (22.9%) were other tumor types. ALK fusions were significantly more frequent in NSCLC (3.1%) than non‐NSCLC (0.2%; p < .0001). Patients with non‐NSCLC tumors harboring fALK were significantly younger (p < .0001) and more often female (p < .0001) than patients with fALK‐positive NSCLC. EML4 was more often the fusion partner in NSCLC (83.5%) versus non‐NSCLC tumors (30.9%; p < .0001).Conclusion.ALK rearrangements can be identified in a wide variety of epithelial and mesenchymal malignancies beyond NSCLC. Anti‐ALK therapies can be effective in non‐NSCLC tumors driven by fALK, and further study of therapies targeting ALK in clinical trials involving a wider variety of cancer types appears warranted.Implications for Practice.Rearrangements involving the ALK gene have been detected in dozens of cancer types using next‐generation sequencing. Patients whose tumors harbor ALK rearrangements or fusions respond to treatment with crizotinib and alectinib, including tumors not normally associated with ALK mutations, such as non‐Langerhans cell histiocytosis or renal cell carcinoma. Comprehensive genomic profiling using next‐generation sequencing can detect targetable ALK fusions irrespective of tumor type or fusions partner.

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In‐Hospital Outcomes of Tumor Lysis Syndrome: A Population‐Based Study Using the National Inpatient Sample

AbstractThe epidemiology and outcomes of tumor lysis syndrome (TLS) are understudied. We used the National Inpatient Sample (NIS), a nationally representative weighted sample of all U.S. hospital discharges, to study outcomes and predictors of mortality in hospitalized patients with TLS. The NIS was queried for patients with a discharge diagnosis of TLS (ICD‐9 code 277.88) from 2010–2013. Baseline characteristics and outcomes were analyzed. A multivariable logistic regression analysis was performed to identify predictors of mortality. From 2010–2013, 28,370 patients were discharged with a diagnosis of TLS. The most common malignancies were non‐Hodgkin lymphoma (30%), solid tumors (20%), acute myeloid leukemia (19%), and acute lymphocytic leukemia (13%). Overall in‐hospital mortality was 21%. The median length of stay was 10 days (IQR 5‐22). Sixty‐nine percent of patients experienced a severe complication, including sepsis (22%, 95% confidence interval [CI] 21–23), dialysis (15%, 95% CI 14–16), acute respiratory failure (23%, 95% CI 22–24), mechanical ventilation (16%, 95% CI 15–17), gastrointestinal hemorrhage (6%, 95% CI 5–7), cerebral hemorrhage (2%, 95% CI 2–3), seizures (1%, 95% CI 0.6–1), and cardiac arrest (2%, 95% CI 2–3). Predictors of mortality were derived from a multivariable logistic regression and included age, Elixhauser comorbidity score, insurance status, teaching versus nonteaching hospital, and cancer type. Predictors of increased length of stay included age, race, teaching versus nonteaching hospital, and cancer type. In the U.S., many patients with TLS develop life‐threatening complications and a quarter die during hospitalization. As more cancer treatments become available, strategies to improve the supportive care of patients with TLS should be a priority.

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Carcinoid Syndrome and Costs of Care During the First Year After Diagnosis of Neuroendocrine Tumors Among Elderly Patients

AbstractBackground.Neuroendocrine tumors (NETs) can secrete hormonal peptides that lead to additional symptom burdens. However, it is largely unknown whether and to what extent the additional symptom burdens translate into higher costs of care. This study aimed to examine the cost pattern of elderly NET patients during the first year of diagnosis, taking into account of the carcinoid syndrome status.Methods.We used Surveillance, Epidemiology, and End Results Medicare data to identify elderly NET patients diagnosed between January 2003 and December 2011. Patients who had at least two claims indicative of carcinoid syndrome during the 3 months before and after the NET diagnosis were considered to have carcinoid syndrome. We adopted a payer's perspective and quantified economic outcomes using the following three measures: (a) total Medicare reimbursement amount, (b) inpatient amount, and (c) outpatient amount. We used a generalized linear model (GLM) to examine the association between syndrome and costs.Results.Our study cohort included 6,749 elderly NET well‐differentiated and moderately differentiated patients. Of these patients, 5,633 (83%) were alive 1 year after diagnosis with continuous enrollment, and 1,116 (17%) died within 1 year. The multivariable GLM showed significant association between the syndrome and higher total, inpatient, and outpatient costs among the group who survived the whole year; the association was insignificant among the group who died within the first year of diagnosis.Conclusion.This population‐based study showed that NET patients with carcinoid syndrome incurred higher costs of care especially among those who survived the first year of diagnosis.Implications for Practice.This is the first population‐based study that examines the health care costs associated with carcinoid syndrome among neuroendocrine tumor patients. Among patients alive throughout the first year, the unadjusted analyses showed that total median monthly costs were above $1,000 higher ($3,801 vs. $2,481) for patients with carcinoid syndrome compared with patients without. A significant association was found between carcinoid syndrome and higher total inpatient and outpatient costs among the group that survived the whole year even after controlling for clinical factors, treatment received, and demographics and neighborhood socioeconomic status; the association was insignificant among the group that died within the first year of diagnosis.

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Salvage Therapy in Advanced Adult Soft Tissue Sarcoma: A Systematic Review and Meta‐Analysis of Randomized Trials

AbstractBackground.Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8–12 months. The role of second‐line therapy has been inconsistently investigated over the last 20 years. This systematic review and meta‐analysis was performed to assess the efficacy of salvage treatment in pretreated adult type STS, gastrointestinal stromal tumor (GIST) excluded.Material and Methods.PubMed, Web of Science, SCOPUS, EMBASE, CINAHL, and The Cochrane Library were searched for randomized phase II/phase III trials exploring second‐ or beyond therapy lines in pretreated metastatic STS. Two independent investigators extracted data; the quality of eligible studies was resolved by consensus. Hazard ratio (HR) of death and progression (OS and progression‐free survival [PFS]) and odds ratio (OR) for response rate (RR) were pooled in a fixed‐ or random‐effects model according to heterogeneity. Study quality was assessed with the Cochrane's risk of bias tool, and publication bias with funnel plots.Results.Overall, 10 randomized trials were selected. The pooled HR for death was 0.81 (95% confidence interval [CI] 0.73–0.9). Second‐line therapy reduced the risk of progression by 49% (HR = 0.51, 95% CI 0.34–0.76). This translated into an absolute benefit in OS and PFS by 3.3 and 1.6 months, respectively. Finally, RR with new agents or chemotherapy doublets translated from 4.3% to 7.6% (OR = 1.78, 95% CI 1.22–2.50).Conclusion.Better survival is achieved in patients treated with salvage therapies (chemotherapy, as single or multiple agents or targeted biological agents). A 3‐months gain in OS and an almost double RR is observed. Second lines also attained a reduction by 50% the risk of progression.Implications for Practice.There is some evidence that salvage therapies after first‐line failure are able to improve outcome in metastatic soft tissue sarcoma (STS). Trabectedin, gemcitabine‐based therapy, and pazopanib are currently approved drugs used after conventional upfront treatment. This meta‐analysis reviews the benefit of new agents used in randomized trials in comparison with no active treatments or older agents for recurrent/progressed STS. The results show that modern drugs confer a statistically significant 3‐month benefit in terms of overall survival, and an increase in response rate. Despite a limited improvement in outcome, currently approved second‐line therapy should be offered to patients with good performance status.

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