Concurrent presentation of an intraductal tubulopapillary neoplasm and intraductal papillary mucinous neoplasm in the branch duct of the pancreas, with a superior mesenteric artery aneurysm: a case report

Abstract

Background

Since the concept of intraductal tubulopapillary neoplasm (ITPN) was introduced in the current World Health Organization classification of tumors, the number of reports of ITPN occurrence has increased gradually. However, ITPN is usually located in the main pancreatic duct, with few reports of a branch duct ITPN. As a result, imaging protocols for the diagnosis of a branch duct ITPN have not been established.

Case presentation

We report a case of a concurrent presentation of a branch duct ITPN and intraductal papillary mucinous neoplasm (IPMN) in the head of the pancreas, with a superior mesenteric artery (SMA) aneurysm. Initially, the cystic masses in the pancreatic head were diagnosed as branch duct IPMNs, with treatment consisting of a pylorus-preserving pancreaticoduodenectomy, in combination with an aneurysmectomy performed for treatment of the SMA aneurysm. Pathological examination confirmed these cysts were a combination of branch-type ITPN and IPMN. The patient recovered from the treatment without complication, with no evidence of recurrence over a period of 34 months post-surgery.

Conclusion

This case report of a synchronous presentation of an ITPN and IPMN indicates the difficulty in differentiating these two types of neoplasms in the branch duct of the pancreatic head.

from Cancer via ola Kala on Inoreader https://ift.tt/2FbYhjy
via IFTTT

Concurrent presentation of an intraductal tubulopapillary neoplasm and intraductal papillary mucinous neoplasm in the branch duct of the pancreas, with a superior mesenteric artery aneurysm: a case report

Abstract

Background

Since the concept of intraductal tubulopapillary neoplasm (ITPN) was introduced in the current World Health Organization classification of tumors, the number of reports of ITPN occurrence has increased gradually. However, ITPN is usually located in the main pancreatic duct, with few reports of a branch duct ITPN. As a result, imaging protocols for the diagnosis of a branch duct ITPN have not been established.

Case presentation

We report a case of a concurrent presentation of a branch duct ITPN and intraductal papillary mucinous neoplasm (IPMN) in the head of the pancreas, with a superior mesenteric artery (SMA) aneurysm. Initially, the cystic masses in the pancreatic head were diagnosed as branch duct IPMNs, with treatment consisting of a pylorus-preserving pancreaticoduodenectomy, in combination with an aneurysmectomy performed for treatment of the SMA aneurysm. Pathological examination confirmed these cysts were a combination of branch-type ITPN and IPMN. The patient recovered from the treatment without complication, with no evidence of recurrence over a period of 34 months post-surgery.

Conclusion

This case report of a synchronous presentation of an ITPN and IPMN indicates the difficulty in differentiating these two types of neoplasms in the branch duct of the pancreatic head.

https://ift.tt/2FbYhjy

Combination Therapy and the Evolution of Resistance: The Theoretical Merits of Synergism and Antagonism in Cancer

The search for effective combination therapies for cancer has focused heavily on synergistic combinations because they exhibit enhanced therapeutic efficacy at lower doses. Although synergism is intuitively attractive, therapeutic success often depends on whether drug resistance develops. The impact of synergistic combinations (vs. antagonistic or additive combinations) on the process of drug-resistance evolution has not been investigated. In this study, we use a simplified computational model of cancer cell numbers in a population of drug-sensitive, singly-resistant, and fully-resistant cells to simulate the dynamics of resistance evolution in the presence of two-drug combinations. When we compared combination therapies administered at the same combination of effective doses, simulations showed synergistic combinations most effective at delaying onset of resistance. Paradoxically, when the therapies were compared using dose combinations with equal initial efficacy, antagonistic combinations were most successful at suppressing expansion of resistant subclones. These findings suggest that, although synergistic combinations could suppress resistance through early decimation of cell numbers (making them "proefficacy" strategies), they are inherently fragile toward the development of single resistance. In contrast, antagonistic combinations suppressed the clonal expansion of singly-resistant cells, making them "antiresistance" strategies. The distinction between synergism and antagonism was intrinsically connected to the distinction between offensive and defensive strategies, where offensive strategies inflicted early casualties and defensive strategies established protection against anticipated future threats. Our findings question the exclusive focus on synergistic combinations and motivate further consideration of nonsynergistic combinations for cancer therapy.Significance: Computational simulations show that if different combination therapies have similar initial efficacy in cancers, then nonsynergistic drug combinations are more likely than synergistic drug combinations to provide a long-term defense against the evolution of therapeutic resistance. Cancer Res; 78(9); 1–13. ©2018 AACR.

from Cancer via ola Kala on Inoreader https://ift.tt/2K97rRN
via IFTTT

Workshop Report for Cancer Research: Defining the Shades of Gy: Utilizing the Biological Consequences of Radiotherapy in the Development of New Treatment Approaches—Meeting Viewpoint

from Cancer via ola Kala on Inoreader https://ift.tt/2vKTCWK
via IFTTT

Combination Therapy and the Evolution of Resistance: The Theoretical Merits of Synergism and Antagonism in Cancer

The search for effective combination therapies for cancer has focused heavily on synergistic combinations because they exhibit enhanced therapeutic efficacy at lower doses. Although synergism is intuitively attractive, therapeutic success often depends on whether drug resistance develops. The impact of synergistic combinations (vs. antagonistic or additive combinations) on the process of drug-resistance evolution has not been investigated. In this study, we use a simplified computational model of cancer cell numbers in a population of drug-sensitive, singly-resistant, and fully-resistant cells to simulate the dynamics of resistance evolution in the presence of two-drug combinations. When we compared combination therapies administered at the same combination of effective doses, simulations showed synergistic combinations most effective at delaying onset of resistance. Paradoxically, when the therapies were compared using dose combinations with equal initial efficacy, antagonistic combinations were most successful at suppressing expansion of resistant subclones. These findings suggest that, although synergistic combinations could suppress resistance through early decimation of cell numbers (making them "proefficacy" strategies), they are inherently fragile toward the development of single resistance. In contrast, antagonistic combinations suppressed the clonal expansion of singly-resistant cells, making them "antiresistance" strategies. The distinction between synergism and antagonism was intrinsically connected to the distinction between offensive and defensive strategies, where offensive strategies inflicted early casualties and defensive strategies established protection against anticipated future threats. Our findings question the exclusive focus on synergistic combinations and motivate further consideration of nonsynergistic combinations for cancer therapy.Significance: Computational simulations show that if different combination therapies have similar initial efficacy in cancers, then nonsynergistic drug combinations are more likely than synergistic drug combinations to provide a long-term defense against the evolution of therapeutic resistance. Cancer Res; 78(9); 1–13. ©2018 AACR.

https://ift.tt/2K97rRN

Workshop Report for Cancer Research: Defining the Shades of Gy: Utilizing the Biological Consequences of Radiotherapy in the Development of New Treatment Approaches—Meeting Viewpoint

https://ift.tt/2vKTCWK

Evaluation of cancer associated DNA copy number events in colorectal (advanced) adenomas

About 5% of colorectal adenomas are estimated to progress to colorectal cancer (CRC). However, it is important to identify which adenomas actually carry a high-risk of progression, because these serve as intermediate endpoints for e.g. screening programs. In clinical practice, adenomas with a size of ≥10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high-risk, although solid evidence for this classification is lacking. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression. We set out to determine the prevalence of CAE's in advanced and non-advanced adenomas. DNA copy number analysis was performed on archival tissues from three independent series of, in total, 297 adenomas (120 non-advanced and 177 advanced) using Multiplex Ligation-dependent Probe Amplification or low-coverage whole genome DNA sequencing. Alterations in two or more CAE's were considered to mark adenomas as high-risk. Two or more CAE's were overall present in 25% (95%CI 19.0-31.8) of advanced adenomas; 23% (11/48), 36% (12/33) and 23% (22/96) of the advanced adenomas in series 1, 2, and 3, respectively, and 1.7% (1/58) and 4.8% (3/62) of the non-advanced adenomas, in series 1 and 2, respectively. The majority of advanced adenomas do not show CAE's, indicating that only a subset of these lesions is to be considered high-risk. Non-advanced adenomas have very low prevalence of CAE's, although those with CAE's should be considered high-risk as well. Specific DNA copy number alterations may better reflect the true progression risk than the advanced adenoma phenotype.

from Cancer via ola Kala on Inoreader https://ift.tt/2vEsBE8
via IFTTT

Cycling Towards Progress: Ribociclib, CDK 4/6 inhibitor for Breast Cancer

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer.

https://ift.tt/2I06F9f

Integrative kinome profiling identifies mTORC1/2 inhibition as treatment strategy in ovarian clear cell carcinoma

Purpose: Advanced stage ovarian clear cell carcinoma (OCCC) is unresponsive to conventional platinum-based chemotherapy. Frequent alterations in OCCC include deleterious mutations in the tumor suppressor ARID1A and activating mutations in the PI3K subunit PIK3CA. In this study, we aimed to identify currently unknown mutated kinases in OCCC patients and test druggability of downstream affected pathways in OCCC models. Experimental Design: In a large set of OCCC patients (n=124), the human kinome (518 kinases) and additional cancer related genes were sequenced and copy number alterations were determined. Genetically characterized OCCC cell lines (n=17) and OCCC patient-derived xenografts (n=3) were used for drug testing of ERBB tyrosine kinase inhibitors erlotinib and lapatinib, the PARP inhibitor olaparib and the mTORC1/2 inhibitor AZD8055. Results: We identified several putative driver mutations in kinases at low frequency that were not previously annotated in OCCC. Combining mutations and copy number alterations, 91% of all tumors are affected in the PI3K/AKT/mTOR pathway, the MAPK pathway or the ERBB family of receptor tyrosine kinases and 82% in the DNA repair pathway. Strong p-S6 staining in OCCC patients suggests high mTORC1/2 activity. We consistently found that the majority of OCCC cell lines are especially sensitive to mTORC1/2 inhibition by AZD8055 and not towards drugs targeting ERBB family of receptor tyrosine kinases or DNA repair signaling. We subsequently demonstrated the efficacy of mTORC1/2 inhibition in all our unique OCCC patient-derived xenograft models. Conclusions: These results propose mTORC1/2 inhibition as an effective treatment strategy in OCCC.

https://ift.tt/2HlX4Ir

Clinicopathological risk factors for an invasive breast cancer recurrence after ductal carcinoma in situ - A nested case-control study

Purpose: Ductal carcinoma in situ (DCIS) is treated to prevent progression to invasive breast cancer. Yet, most lesions will never progress, implying that overtreatment exists. Therefore, we aimed to identify factors distinguishing harmless from potentially hazardous DCIS using a nested case-control study. Experimental Design: We conducted a case-control study nested in a population-based cohort of DCIS patients treated with breast conserving surgery (BCS) alone (n=2,658) between 1989-2005. We compared clinical, pathological, and immunohistochemical DCIS characteristics of 200 women who subsequently developed ipsilateral invasive breast cancer (iIBC; cases) and 474 women who did not (controls), in a matched setting. Median follow-up time was 12.0 years (interquartile range 9.0-15.3). Conditional logistic regression models, were used to assess associations of various factors with subsequent iIBC risk after primary DCIS. Results: High COX-2 protein expression showed the strongest association with subsequent iIBC (odds ratio [OR]=2.97, 95% confidence interval [95%CI] 1.72-5.10). In addition, HER2 overexpression (OR=1.56, 95%CI 1.05-2.31) and presence of periductal fibrosis (OR=1.44, 95%CI 1.01-2.06) were associated with subsequent iIBC risk. Patients with HER2+/COX-2high DCIS had a 4-fold higher risk of subsequent iIBC (vs. HER2-/COX-2low DCIS), and an estimated 22.8% cumulative risk of developing subsequent iIBC at 15 years. Conclusions: With this unbiased study design and representative group of DCIS patients treated by BCS alone, COX-2, HER2, and periductal fibrosis were revealed as promising markers predicting progression of DCIS into iIBC. Validation will be done in independent data sets. Ultimately, this will aid individual risk stratification of women with primary DCIS.

https://ift.tt/2HUOEZI

21-gene recurrence score assay predicts benefit of post-mastectomy radiotherapy in T1-2 N1 breast cancer

Purpose: Post-mastectomy radiotherapy (PMRT) yields improvements in both locoregional control and overall survival (OS) for women with T1-2 N1 breast cancer. The value of PMRT in this population has been questioned given advances in systemic therapy. The 21-gene Recurrence Score (RS) assay was evaluated as a predictor of OS among women with T1-2 N1 breast cancer who received or did not receive PMRT. Experimental Design: An observational cohort study was performed on women with T1-2 N1 estrogen receptor-positive breast cancer from the National Cancer Database (NCDB) and, as a validation cohort, from the Surveillance, Epidemiology, and End Results (SEER) registry who underwent mastectomy and were evaluated for RS. Multivariable parametric accelerated failure time models were used to estimate associations of RS and PMRT with OS using propensity score-adjusted matched cohorts. Results: In both the NCDB (N=7,332) and SEER (N=3,087) cohorts, there was a significant interaction of RS and PMRT with OS (P=0.009 and P=0.03, respectively). PMRT was associated with longer OS in women with a low RS (NCDB: time-ratio (TR)=1.70, 95% CI=1.30-2.22, P<0.001; SEER: TR=1.85, 95% CI=1.33-2.57, P<0.001), but not in women with an intermediate RS (NCDB: TR=0.89, 95% CI=0.69-1.14, P=0.35; SEER: TR=0.84, 95% CI=0.62-1.14, P=0.26), or a high RS (NCDB: TR=1.10, 95% CI=0.91-1.34, P=0.33; SEER: TR=0.79, CI=0.50-1.23, P=0.28). Conclusions: Longer survival associated with PMRT was limited to women with a low RS. PMRT may confer the greatest OS benefit for patients at lowest risk of distant recurrence. These results caution against omission of PMRT among women with low RS.

https://ift.tt/2HmcIDL

A model of overall survival predicts treatment outcomes with atezolizumab vs chemotherapy in non-small cell lung cancer based on early tumor kinetics

Purpose: Standard endpoints often poorly predict overall survival (OS) with immunotherapies. We investigated the predictive performance of model-based tumor growth inhibition (TGI) metrics using data from atezolizumab clinical trials in patients with non-small cell lung cancer. Methods: OS benefit with atezolizumab vs docetaxel was observed in both POPLAR (phase II) and OAK (phase III) although progression-free survival was similar between arms. A multivariate model linking baseline patient characteristics and on-treatment tumor growth rate constant (KG), estimated using time profiles of sum of longest diameters (RECIST 1.1) to OS, was developed using POPLAR data. The model was evaluated to predict OAK outcome based on estimated KG at TGI data cutoffs ranging from 10 to 122 weeks. Results: In POPLAR, TGI profiles in both arms crossed at 25 weeks, with more shrinkage with docetaxel and slower KG with atezolizumab. A log-normal OS model, with albumin and number of metastatic sites as independent prognostic factors and estimated KG, predicted OS hazard ratio (HR) in sub-populations of patients with varying baseline PD-L1 expression in both POPLAR and OAK: model-predicted OAK HR (95% prediction interval): 0.73 (0.63-0.85) vs 0.73 observed. The POPLAR OS model predicted greater than 97% chance of success of OAK (significant OS HR, P < 0.05) from the 40-week data cutoff onward with 50% of the total number of tumor assessments when a successful study was predicted from 70 weeks onward based on observed OS. Conclusions: KG has potential as a model-based early endpoint to inform decisions in cancer immunotherapy studies.

https://ift.tt/2HVFQ5W

Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients With Melanoma Treated With Pembrolizumab

Purpose: To assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). Experimental Design: BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Results: Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites) (all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs 23%; P < 0.001) and improved OS (hazard ratio, 0.38; P < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. Conclusions: BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma.

https://ift.tt/2Fcaipg

Cycling Towards Progress: Ribociclib, CDK 4/6 inhibitor for Breast Cancer

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer.

from Cancer via ola Kala on Inoreader https://ift.tt/2I06F9f
via IFTTT

Integrative kinome profiling identifies mTORC1/2 inhibition as treatment strategy in ovarian clear cell carcinoma

Purpose: Advanced stage ovarian clear cell carcinoma (OCCC) is unresponsive to conventional platinum-based chemotherapy. Frequent alterations in OCCC include deleterious mutations in the tumor suppressor ARID1A and activating mutations in the PI3K subunit PIK3CA. In this study, we aimed to identify currently unknown mutated kinases in OCCC patients and test druggability of downstream affected pathways in OCCC models. Experimental Design: In a large set of OCCC patients (n=124), the human kinome (518 kinases) and additional cancer related genes were sequenced and copy number alterations were determined. Genetically characterized OCCC cell lines (n=17) and OCCC patient-derived xenografts (n=3) were used for drug testing of ERBB tyrosine kinase inhibitors erlotinib and lapatinib, the PARP inhibitor olaparib and the mTORC1/2 inhibitor AZD8055. Results: We identified several putative driver mutations in kinases at low frequency that were not previously annotated in OCCC. Combining mutations and copy number alterations, 91% of all tumors are affected in the PI3K/AKT/mTOR pathway, the MAPK pathway or the ERBB family of receptor tyrosine kinases and 82% in the DNA repair pathway. Strong p-S6 staining in OCCC patients suggests high mTORC1/2 activity. We consistently found that the majority of OCCC cell lines are especially sensitive to mTORC1/2 inhibition by AZD8055 and not towards drugs targeting ERBB family of receptor tyrosine kinases or DNA repair signaling. We subsequently demonstrated the efficacy of mTORC1/2 inhibition in all our unique OCCC patient-derived xenograft models. Conclusions: These results propose mTORC1/2 inhibition as an effective treatment strategy in OCCC.

from Cancer via ola Kala on Inoreader https://ift.tt/2HlX4Ir
via IFTTT

Clinicopathological risk factors for an invasive breast cancer recurrence after ductal carcinoma in situ - A nested case-control study

Purpose: Ductal carcinoma in situ (DCIS) is treated to prevent progression to invasive breast cancer. Yet, most lesions will never progress, implying that overtreatment exists. Therefore, we aimed to identify factors distinguishing harmless from potentially hazardous DCIS using a nested case-control study. Experimental Design: We conducted a case-control study nested in a population-based cohort of DCIS patients treated with breast conserving surgery (BCS) alone (n=2,658) between 1989-2005. We compared clinical, pathological, and immunohistochemical DCIS characteristics of 200 women who subsequently developed ipsilateral invasive breast cancer (iIBC; cases) and 474 women who did not (controls), in a matched setting. Median follow-up time was 12.0 years (interquartile range 9.0-15.3). Conditional logistic regression models, were used to assess associations of various factors with subsequent iIBC risk after primary DCIS. Results: High COX-2 protein expression showed the strongest association with subsequent iIBC (odds ratio [OR]=2.97, 95% confidence interval [95%CI] 1.72-5.10). In addition, HER2 overexpression (OR=1.56, 95%CI 1.05-2.31) and presence of periductal fibrosis (OR=1.44, 95%CI 1.01-2.06) were associated with subsequent iIBC risk. Patients with HER2+/COX-2high DCIS had a 4-fold higher risk of subsequent iIBC (vs. HER2-/COX-2low DCIS), and an estimated 22.8% cumulative risk of developing subsequent iIBC at 15 years. Conclusions: With this unbiased study design and representative group of DCIS patients treated by BCS alone, COX-2, HER2, and periductal fibrosis were revealed as promising markers predicting progression of DCIS into iIBC. Validation will be done in independent data sets. Ultimately, this will aid individual risk stratification of women with primary DCIS.

from Cancer via ola Kala on Inoreader https://ift.tt/2HUOEZI
via IFTTT

21-gene recurrence score assay predicts benefit of post-mastectomy radiotherapy in T1-2 N1 breast cancer

Purpose: Post-mastectomy radiotherapy (PMRT) yields improvements in both locoregional control and overall survival (OS) for women with T1-2 N1 breast cancer. The value of PMRT in this population has been questioned given advances in systemic therapy. The 21-gene Recurrence Score (RS) assay was evaluated as a predictor of OS among women with T1-2 N1 breast cancer who received or did not receive PMRT. Experimental Design: An observational cohort study was performed on women with T1-2 N1 estrogen receptor-positive breast cancer from the National Cancer Database (NCDB) and, as a validation cohort, from the Surveillance, Epidemiology, and End Results (SEER) registry who underwent mastectomy and were evaluated for RS. Multivariable parametric accelerated failure time models were used to estimate associations of RS and PMRT with OS using propensity score-adjusted matched cohorts. Results: In both the NCDB (N=7,332) and SEER (N=3,087) cohorts, there was a significant interaction of RS and PMRT with OS (P=0.009 and P=0.03, respectively). PMRT was associated with longer OS in women with a low RS (NCDB: time-ratio (TR)=1.70, 95% CI=1.30-2.22, P<0.001; SEER: TR=1.85, 95% CI=1.33-2.57, P<0.001), but not in women with an intermediate RS (NCDB: TR=0.89, 95% CI=0.69-1.14, P=0.35; SEER: TR=0.84, 95% CI=0.62-1.14, P=0.26), or a high RS (NCDB: TR=1.10, 95% CI=0.91-1.34, P=0.33; SEER: TR=0.79, CI=0.50-1.23, P=0.28). Conclusions: Longer survival associated with PMRT was limited to women with a low RS. PMRT may confer the greatest OS benefit for patients at lowest risk of distant recurrence. These results caution against omission of PMRT among women with low RS.

from Cancer via ola Kala on Inoreader https://ift.tt/2HmcIDL
via IFTTT

A model of overall survival predicts treatment outcomes with atezolizumab vs chemotherapy in non-small cell lung cancer based on early tumor kinetics

Purpose: Standard endpoints often poorly predict overall survival (OS) with immunotherapies. We investigated the predictive performance of model-based tumor growth inhibition (TGI) metrics using data from atezolizumab clinical trials in patients with non-small cell lung cancer. Methods: OS benefit with atezolizumab vs docetaxel was observed in both POPLAR (phase II) and OAK (phase III) although progression-free survival was similar between arms. A multivariate model linking baseline patient characteristics and on-treatment tumor growth rate constant (KG), estimated using time profiles of sum of longest diameters (RECIST 1.1) to OS, was developed using POPLAR data. The model was evaluated to predict OAK outcome based on estimated KG at TGI data cutoffs ranging from 10 to 122 weeks. Results: In POPLAR, TGI profiles in both arms crossed at 25 weeks, with more shrinkage with docetaxel and slower KG with atezolizumab. A log-normal OS model, with albumin and number of metastatic sites as independent prognostic factors and estimated KG, predicted OS hazard ratio (HR) in sub-populations of patients with varying baseline PD-L1 expression in both POPLAR and OAK: model-predicted OAK HR (95% prediction interval): 0.73 (0.63-0.85) vs 0.73 observed. The POPLAR OS model predicted greater than 97% chance of success of OAK (significant OS HR, P < 0.05) from the 40-week data cutoff onward with 50% of the total number of tumor assessments when a successful study was predicted from 70 weeks onward based on observed OS. Conclusions: KG has potential as a model-based early endpoint to inform decisions in cancer immunotherapy studies.

from Cancer via ola Kala on Inoreader https://ift.tt/2HVFQ5W
via IFTTT

Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients With Melanoma Treated With Pembrolizumab

Purpose: To assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). Experimental Design: BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Results: Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites) (all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs 23%; P < 0.001) and improved OS (hazard ratio, 0.38; P < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. Conclusions: BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma.

from Cancer via ola Kala on Inoreader https://ift.tt/2Fcaipg
via IFTTT

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study, Published online: 24 April 2018; doi:10.1038/s41416-018-0052-7

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

https://ift.tt/2HJDMAc

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study, Published online: 24 April 2018; doi:10.1038/s41416-018-0052-7

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

from Cancer via ola Kala on Inoreader https://ift.tt/2HJDMAc
via IFTTT

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

from Cancer via ola Kala on Inoreader https://ift.tt/2Hpk4WY
via IFTTT

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

https://ift.tt/2Hpk4WY

The Impact of Hormonal Contraceptives on Breast Cancer Pathology

Abstract

This retrospective case series study, using data obtained through questionnaires and histopathological diagnoses from 656 patients enrolled in the Department of Defense (DoD) Clinical Breast Care Project (CBCP), evaluated associations between hormonal contraceptive use and breast cancer pathology including benign breast pathologies. Three combination hormonal contraceptive agents (COCs) Lo Ovral (LO), Ortho Novum (ON), and Ortho Tri-Cyclen (OTC) were evaluated as they represented the most commonly used hormonal contraceptives in our cohort. The results of this study suggest that the ever use of LO + ON + OTC does not influence the overall incidence of benign breast condition or malignant disease compared to other COCs; however, patients that have used OTC had an association with a diagnosis of benign or luminal A pathologies whereas ON was associated with a diagnosis of benign and DCIS; LO showed no association with any diagnosis—benign or malignant. Patients that have used LO or ON were more likely to be diagnosed with breast cancer at age ≥ 40 years whereas patients that had ever used OTC were likely to be diagnosed before the age of 40. Caucasians were less likely to have used OTC and more likely to have used ON; however, use of either hormonal agent positively correlated with premenopausal status at diagnosis and having a benign condition. Age at diagnosis, ethnicity, BMI, family history, menstruation status, and duration of use were all independent predictors of different histopathological subtypes. We conclude that patient-specific variables should be considered when deciding on which type of hormonal contraceptive to use to minimize the risk of developing breast cancer or a breast-related pathology.

from Cancer via ola Kala on Inoreader https://ift.tt/2HWYpXy
via IFTTT

The Impact of Hormonal Contraceptives on Breast Cancer Pathology

Abstract

This retrospective case series study, using data obtained through questionnaires and histopathological diagnoses from 656 patients enrolled in the Department of Defense (DoD) Clinical Breast Care Project (CBCP), evaluated associations between hormonal contraceptive use and breast cancer pathology including benign breast pathologies. Three combination hormonal contraceptive agents (COCs) Lo Ovral (LO), Ortho Novum (ON), and Ortho Tri-Cyclen (OTC) were evaluated as they represented the most commonly used hormonal contraceptives in our cohort. The results of this study suggest that the ever use of LO + ON + OTC does not influence the overall incidence of benign breast condition or malignant disease compared to other COCs; however, patients that have used OTC had an association with a diagnosis of benign or luminal A pathologies whereas ON was associated with a diagnosis of benign and DCIS; LO showed no association with any diagnosis—benign or malignant. Patients that have used LO or ON were more likely to be diagnosed with breast cancer at age ≥ 40 years whereas patients that had ever used OTC were likely to be diagnosed before the age of 40. Caucasians were less likely to have used OTC and more likely to have used ON; however, use of either hormonal agent positively correlated with premenopausal status at diagnosis and having a benign condition. Age at diagnosis, ethnicity, BMI, family history, menstruation status, and duration of use were all independent predictors of different histopathological subtypes. We conclude that patient-specific variables should be considered when deciding on which type of hormonal contraceptive to use to minimize the risk of developing breast cancer or a breast-related pathology.

https://ift.tt/2HWYpXy

A novel voxel based homogeneity index: Rationale and clinical implications for whole-brain radiation therapy

A homogeneity index (HI) measures the uniformity of a dose distribution within a given target volume. Traditional HIs only use a limited number of dose–volume histogram data-points for calculation. A voxel-based homogeneity index (VHI) is proposed which utilizes the entire information of the three-dimensional dose distribution. We compared the VHI with existing HIs and analyzed if VHI results were associated with treatment outcomes in patients who underwent therapeutic WBRT.

https://ift.tt/2HVJ7Sy

Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors

Objectives: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy. Methods: Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence. Results: Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8). Conclusions: Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

from Cancer via ola Kala on Inoreader https://ift.tt/2HWlSb9
via IFTTT

Survival of Patients With Multiple Intracranial Metastases Treated With Stereotactic Radiosurgery: Does the Number of Tumors Matter?

Background: Defining prognostic factors is a crucial initial step for determining the management of patients with brain metastases. Randomized trials assessing radiosurgery have commonly limited inclusion criteria to 1 to 4 brain metastases, in part due to multiple retrospective studies reporting on the number of brain metastases as a prognostic indicator. The present study reports on the survival of patients with 1 to 4 versus ≥5 brain metastases treated with radiosurgery. Methods: We evaluated a retrospective multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or Cyberknife) between 2001 and 2014. A total of 243 patients were included in the analysis. Patients with 1 to 4 brain metastases were compared with patients with ≥5 brain metastases using a standard statistical analysis. Cox hazard regression was used to construct a multivariable model of overall survival (OS). To find covariates that best separate the data at each split, a machine learning technique Chi-squared Automated Interaction Detection tree was utilized. Results: On Pearson correlation, systemic disease status, number of intracranial metastases, and overall burden of disease (number of major involved organ systems) were found to be highly correlated (P

from Cancer via ola Kala on Inoreader https://ift.tt/2HRV0sJ
via IFTTT

Retrospective Analysis of Cisplatin Nephrotoxicity in Patients With Head and Neck Cancer Receiving Outpatient Treatment With Concurrent High-dose Cisplatin and Radiotherapy

Objectives: Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck (SCCHN), with nephrotoxicity considered the dose-limiting toxicity. The purpose of our study was to propose an outpatient high-dose cisplatin protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with SCCHN treated with concurrent radiotherapy. Materials and Methods: We retrospectively evaluated 82 SCCHN patients treated with outpatient high-dose cisplatin concurrent with radiotherapy at our institution. Acute kidney injury (AKI) and chronic kidney disease were defined by Kidney Disease Improving Global Outcomes criteria. Associated factors were identified using analysis of covariance models for categorical variables and adjusted Pearson correlations for continuous variables. Results: The incidence of AKI during treatment was 34.2%. With a median follow-up of 25.7 months, the average decrease in estimated glomerular filtration rate was 12.57 mL/min/1.73 m2 (SD=18.58). At 1 year and at last follow-up, 5.4% and 4.4% of patients had estimated glomerular filtration rate

from Cancer via ola Kala on Inoreader https://ift.tt/2F8dW3D
via IFTTT

Targeted Prostate Biopsy Gleason Score Heterogeneity and Implications for Risk Stratification

Objectives: To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification. Methods: An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal–ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with ≥2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared. Results: Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had ≥2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases. Conclusions: Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice.

from Cancer via ola Kala on Inoreader https://ift.tt/2HUL0Pn
via IFTTT

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer

Objectives: Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Methods: Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Results: Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Conclusions: Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

from Cancer via ola Kala on Inoreader https://ift.tt/2HmGXKF
via IFTTT

Comparison of Demographics, Tumor Characteristics, and Survival Between Pancreatic Adenocarcinomas and Pancreatic Neuroendocrine Tumors: A Population-based Study

Objective: The objective of this study is to compare the incidence, demographics, tumor characteristics, and survival between patients with pancreatic neuroendocrine tumors (PNETs) and pancreatic adenocarcinomas. Materials and Methods: Between 2004 and 2012, all cases of pancreatic adenocarcinomas and PNETs were extracted from the population-based cancer registries of the Surveillance Epidemiology and End Results program. To identify the cases, a combination of topographical and histology codes based on ICD-O-3 were used. Incidence, demographics, tumor characteristics, and survival was then compared between these 2 histologic subtypes of pancreatic cancer. Results: A total of 57,688 patients with pancreatic cancer were identified, of which 53,753 (93%) had pancreatic adenocarcinoma and 3935 (7%) had PNET. The overall age-adjusted incidence of PNETs between 2004 and 2012 was 0.52 per 100,000 per year, whereas that for pancreatic adenocarcinomas during the same period was 7.34 per 100,000 per year. PNETs had a significantly younger median age at diagnosis (61 vs. 69 y). A significant proportion of PNETs were diagnosed at stage I (20.5% vs. 6.0%) and were well differentiated (32.8% vs. 4.5%) compared with adenocarcinomas. Five-year cause-specific survival was 51.3% and 5.0% for PNETs and pancreatic adenocarcinomas, respectively. In multivariate analysis, pancreatic adenocarcinomas had a hazard ratio for death of 4.02 (95% confidence interval, 3.79-4.28) when compared with PNETs. Conclusions: PNETs present with favorable features such as higher proportion of early-stage tumor, higher proportion of well differentiated tumors, and younger age at diagnosis. PNETs have a significantly better survival than pancreatic adenocarcinomas even after adjusting for age, sex, race, site, grade, and stage.

from Cancer via ola Kala on Inoreader https://ift.tt/2HTN7mO
via IFTTT

Locally Advanced Cervical Cancer: Outcomes With Variable Adherence to Treatment

Objective: Adherence to treatment regimen and schedule is recommended to improve control of disease and overall survival (OS) in locally advanced cervical cancer. However, treatment-related toxicities and patient and physician factors all impact timely completion of treatment. We sought to correlate adherence to treatment plan with survival and toxicities of patients treated for locally advanced cervical cancer. Materials and Methods: A retrospective review of patients treated for advanced cervical cancer at our institution between 2003 and 2011 was performed. Demographics, clinicopathologic variables, treatment, and disease outcomes were collected. Endpoints of disease outcome were disease-free survival and OS. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: A total of 162 patients met the inclusion criteria and were included in study analysis. A total of 95% of patients were treated with both radiation and concurrent chemotherapy. Mean radiation dose to point A was 72 Gy. In total, 77% had complete response to primary therapy. Severe (grade 3/4) late radiation toxicities were seen in 10.5% of patients. Stage and total radiation dose to point A were significant predictors of survival for the entire cohort. Among patients receiving at least 72 Gy and brachytherapy, duration of treatment was significantly associated with both disease-free survival and OS. Conclusions: Adherence to both optimal treatment time and radiation dose is significantly associated with improved survival. Total radiation dose is an independent predictor of survival among patients with locally advanced cervical cancer.

from Cancer via ola Kala on Inoreader https://ift.tt/2F8tQLb
via IFTTT

Utilization of Postoperative Chemoradiotherapy Among Women in the United States With High-risk Cervical Cancer

Objective: Prospective randomized data demonstrates that chemoradiotherapy (CRT) improves overall survival in women with high-risk pathologic features following radical hysterectomy. Despite this, not all high-risk patients receive adjuvant CRT and the patterns of care in this patient population are unknown. We sought to investigate the rates of adjuvant therapy utilization through analysis of the National Cancer Database. Materials and Methods: The National Cancer Database was queried for women with cervical cancer treated initially with hysterectomy from 2002 to 2012. Patients without high-risk pathologic features were excluded: pN+, positive surgical margins, and parametrial invasion (Peters' criteria). Among the 5947 evaluable patients, univariable analysis and multivariable analysis were performed to investigate potential factors associated with CRT utilization and overall survival following diagnosis. Results: Adjuvant CRT was performed in 41.8% of women and adjuvant radiotherapy, chemotherapy, and no adjuvant therapy was utilized in 9.8%, 23.6%, and 24.8% of women, respectively. On multivariable analysis, CRT utilization was associated with younger age, race, lower facility volume, pN+, parametrial invasion, and a negative surgical margin. Residence distance to treating facility, year of diagnosis, household income, insurance status, and facility type did not predict for CRT utilization. Conclusions: Despite level I evidence supporting its use, less than half of women in this large US cohort with high-risk cervical cancer received adjuvant CRT. Use of adjuvant CRT for women did not significantly increase between 2002 and 2012. Patient age, race, and pathologic risk factors were associated with use of adjuvant CRT.

from Cancer via ola Kala on Inoreader https://ift.tt/2F8tQe9
via IFTTT

Perioperative Mortality in Nonelderly Adult Patients With Cancer: A Population-based Study Evaluating Health Care Disparities in the United States According to Insurance Status

Objectives: The purpose of this study was to evaluate whether insurance status predicts for perioperative mortality (death within 30 d of cancer-directed surgery) for the 20 most common surgically treated cancers. Methods: The SEER database was examined for the 20 most common surgically resected cancers and included nonelderly adults, aged 18 to 64 years. The database was queried from 2007 to 2011, with a total of 506,722 patients included in the analysis. Results: Insurance status for all patients were the following: non-Medicaid insurance (83%), any Medicaid (10%), uninsured (4%), and unknown (3%). In univariate analyses, predictors for perioperative mortality included insurance status (P

from Cancer via ola Kala on Inoreader https://ift.tt/2HTN6iK
via IFTTT

Secondary Surgery Versus Chemotherapy for Recurrent Ovarian Cancer

Objective: The best course of treatment for recurrent ovarian cancer is uncertain. We sought to determine whether secondary cytoreductive surgery for first recurrence of ovarian cancer improves overall survival compared with other treatments. Materials and Methods: We assessed survival using Surveillance, Epidemiology and End Results-Medicare data for advanced stage ovarian cancer cases diagnosed from January 1, 1997 to December 31, 2007 with survival data through 2010 using multinomial propensity weighted finite mixture survival regression models to distinguish true from misclassified recurrences. Of 35,995 women ages 66 years and older with ovarian cancer, 3439 underwent optimal primary debulking surgery with 6 cycles of chemotherapy; 2038 experienced a remission. Results: One thousand six hundred thirty-five of 2038 (80%) women received treatment for recurrence of whom 72% were treated with chemotherapy only, 16% with surgery and chemotherapy and 12% received hospice care. Median survival of women treated with chemotherapy alone, surgery and chemotherapy, or hospice care was 4.1, 5.4, and 2.2 years, respectively (P

from Cancer via ola Kala on Inoreader https://ift.tt/2Fe1wY8
via IFTTT

Vulvar Recurrences After Intensity-modulated Radiation Therapy for Squamous Cell Carcinoma of the Anus

Objectives: The objective is to determine localregional control (LRC), distant metastasis free survival, disease-free survival, overall survival (OS), and toxicity for patients with squamous cell carcinoma of the anus treated with definitive chemotherapy and intensity-modulated radiation therapy (IMRT). Materials and Methods: We conducted a retrospective review of patients treated using IMRT for squamous cell carcinoma of the anus at our institution since 2005. Patients with local recurrences were identified and reviewed. The Kaplan-Meier curves were used for LRC and OS. Results: From 2005 to 2014, 52 patients were treated with IMRT-based chemoradiation for squamous cell carcinoma of the anus. Median dose to the primary tumor was 54 Gy. LRC, distant metastasis free survival, OS, and disease-free survival were 92.3%, 88.5%, 86.5%, and 84.6%, respectively, with a median follow-up of 20 months. Two local failures occurred at the anal primary site and 2 in the vulva. Despite subsequent palliative radiotherapy and chemotherapy, neither patient with a vulvar recurrence achieved disease control. Conclusions: In a cohort of patients treated with IMRT-based chemoradiation, 2 vulvar recurrences were identified within the avoided external genitalia despite limited recurrence rates within the cohort overall. This experience suggests that for patients with a locally advanced primary tumor and bulky bilateral inguinal or pelvic disease, the in-transit vulvar dermal lymphatics may be at risk for subclinical involvement and subsequent recurrence. If substantiated by a similar pattern of recurrence at other institutions, the external genitalia may need to be reclassified from an avoidance structure to a clinical treatment volume in patients with locally advanced anal cancer.

from Cancer via ola Kala on Inoreader https://ift.tt/2HVMER8
via IFTTT

Malignant Peripheral Nerve Sheath Tumors: A Single Institution’s Experience Using Combined Surgery and Radiation Therapy

Purpose: The purpose of this study is to investigate local control (LC), survival outcomes, and associated prognostic factors for patients with malignant peripheral nerve sheath tumors (MPNSTs) treated with combined surgery and radiation therapy (RT). Methods: We reviewed the medical records of 71 consecutive patients treated with surgery and RT for localized MPNST between 1965 and 2012. Preoperative RT was used to treat 23 patients (32%) to a median dose of 50 Gy (range, 50 to 60 Gy), whereas 48 (68%) received postoperative RT to a median dose of 64 Gy (range, 45 to 70 Gy). Results: Median follow-up for living patients was 118 months (range, 21 to 512 mo). The 5-year LC, distant metastatic free survival, and disease-specific survival rates were 84%, 62%, and 66%, respectively. To identify predictors of outcome, several multivariate models were constructed: (1) positive/uncertain surgical margin status was the only factor adversely associated local relapse at 5 years (28% vs. 5% for negative margins; P=0.02; hazard ratios 5.92; 95% confidence interval, 1.3-27.4). (2) No factors were significantly associated with distant metastatic free survival. Of the 35 patients (49%) who sustained disease relapse, only 3 were ultimately salvaged. Only 2 patients had grade 2 late toxicities (necrosis, fibrosis) based on Common Terminology Criteria for Adverse Events version 4.03 criteria, and 1 patient had grade 1 edema. Conclusions: Combination therapy with surgery and RT provides favorable LC. Distant recurrences, however, continue to be challenging with limited salvage success at the time of relapse.

from Cancer via ola Kala on Inoreader https://ift.tt/2Fe1oYE
via IFTTT

A Pooled Analysis of Biochemical Failure in Intermediate-risk Prostate Cancer Following Definitive Stereotactic Body Radiotherapy (SBRT) or High-Dose-Rate Brachytherapy (HDR-B) Monotherapy

Objectives: To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy. Materials and Methods: A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel χ2 metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure. Results: The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ≤3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS. Conclusions: With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.

from Cancer via ola Kala on Inoreader https://ift.tt/2HRUYB7
via IFTTT

Disparity in Outcomes for Adolescent and Young Adult Patients Diagnosed With Pediatric Solid Tumors Across 4 Decades

Objective: Cancer mortality is a leading cause of disease-related death in the adolescent and young adult (AYA) population. Compared with older and younger patients, AYA patients often experience worse cancer-specific outcomes. Here, we compare AYA and pediatric overall survival (OS) in the most common pediatric extracranial solid tumors. Materials and Methods: Using the US Surveillance, Epidemiology, and End Results database, we studied patients (age, 0 to 39 y) diagnosed with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, and Wilms tumor. Results: A total of 12,375 patients (age, 0 to 39 y) were diagnosed between 1973 and 2010 (8247 pediatric and 4128 AYA patients). AYA patients with rhabdomyosarcoma and Ewing sarcoma were more likely to present with metastatic disease. OS was significantly worse in the AYA cohort for all tumor types (P

from Cancer via ola Kala on Inoreader https://ift.tt/2FacFco
via IFTTT

Impact of Staging With Positron-emission Tomography (PET) and Comorbidities on Management and Survival of American Veterans With Stage I-III Non–Small Cell Lung Cancer

Objectives: The extent of whether staging by fluorodeoxyglucose positron-emission tomography (PET) impacts outcomes in American Veterans with stage I-III non–small-cell lung cancer (NSCLC) is unknown. We investigated impact of fluorodeoxyglucose PET staging and age-adjusted comorbidities (AACs) on management and survival of NSCLC in this group. Materials and Methods: We performed a retrospective review to identify with NSCLC who underwent initial PET scan and received care at the Ann Arbor Veterans Hospital between 2005 and 2010. Survival outcomes were estimated by Kaplan-Meier methods, quantile regressions, and Cox proportional hazards models, after accounting for age at diagnosis, sex, AAC, and initial treatment. Results: The number of PET scans increased from 0 in 2005 to 66 in 2010. There were 170 men, 4 women, median age 64 years. Median AAC score was 4. In CS I (n=54), initial PET upstaged 5 patients. Median survival for no change in PET stage was 27.43 versus 67 months for upstaged patients (P=0.034). For CS II (n=15), initial PET scan upstaged 1 patient. Median survival for no change in PET stage was 16.53 versus 2.8 months for upstaged patient (P=0.335). For CS III (n=104), PET scan upstaged 20 patients. Median survival for no change in PET stage was 13.3 versus 3.8 months for upstaged patients (P=0.016). Conclusions: PET scans resulted in upstaging in 15% in CS I-III NSCLC. AAC scores dictated therapy decisions and outcomes more than PET staging. Veterans had lower 5-year survival rates (26.3%, 15.8%/13.4%) compared with 53% and 27% in age/sex/time-period matched SEER data for stage I-II/III NSCLC.

from Cancer via ola Kala on Inoreader https://ift.tt/2HVbUa4
via IFTTT

Survival of Patients With Multiple Intracranial Metastases Treated With Stereotactic Radiosurgery: Does the Number of Tumors Matter?

Background: Defining prognostic factors is a crucial initial step for determining the management of patients with brain metastases. Randomized trials assessing radiosurgery have commonly limited inclusion criteria to 1 to 4 brain metastases, in part due to multiple retrospective studies reporting on the number of brain metastases as a prognostic indicator. The present study reports on the survival of patients with 1 to 4 versus ≥5 brain metastases treated with radiosurgery. Methods: We evaluated a retrospective multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or Cyberknife) between 2001 and 2014. A total of 243 patients were included in the analysis. Patients with 1 to 4 brain metastases were compared with patients with ≥5 brain metastases using a standard statistical analysis. Cox hazard regression was used to construct a multivariable model of overall survival (OS). To find covariates that best separate the data at each split, a machine learning technique Chi-squared Automated Interaction Detection tree was utilized. Results: On Pearson correlation, systemic disease status, number of intracranial metastases, and overall burden of disease (number of major involved organ systems) were found to be highly correlated (P

https://ift.tt/2HRV0sJ

Retrospective Analysis of Cisplatin Nephrotoxicity in Patients With Head and Neck Cancer Receiving Outpatient Treatment With Concurrent High-dose Cisplatin and Radiotherapy

Objectives: Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck (SCCHN), with nephrotoxicity considered the dose-limiting toxicity. The purpose of our study was to propose an outpatient high-dose cisplatin protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with SCCHN treated with concurrent radiotherapy. Materials and Methods: We retrospectively evaluated 82 SCCHN patients treated with outpatient high-dose cisplatin concurrent with radiotherapy at our institution. Acute kidney injury (AKI) and chronic kidney disease were defined by Kidney Disease Improving Global Outcomes criteria. Associated factors were identified using analysis of covariance models for categorical variables and adjusted Pearson correlations for continuous variables. Results: The incidence of AKI during treatment was 34.2%. With a median follow-up of 25.7 months, the average decrease in estimated glomerular filtration rate was 12.57 mL/min/1.73 m2 (SD=18.58). At 1 year and at last follow-up, 5.4% and 4.4% of patients had estimated glomerular filtration rate

https://ift.tt/2F8dW3D

Targeted Prostate Biopsy Gleason Score Heterogeneity and Implications for Risk Stratification

Objectives: To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification. Methods: An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal–ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with ≥2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared. Results: Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had ≥2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases. Conclusions: Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice.

https://ift.tt/2HUL0Pn

Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer

Objectives: Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Methods: Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Results: Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Conclusions: Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

https://ift.tt/2HmGXKF

Comparison of Demographics, Tumor Characteristics, and Survival Between Pancreatic Adenocarcinomas and Pancreatic Neuroendocrine Tumors: A Population-based Study

Objective: The objective of this study is to compare the incidence, demographics, tumor characteristics, and survival between patients with pancreatic neuroendocrine tumors (PNETs) and pancreatic adenocarcinomas. Materials and Methods: Between 2004 and 2012, all cases of pancreatic adenocarcinomas and PNETs were extracted from the population-based cancer registries of the Surveillance Epidemiology and End Results program. To identify the cases, a combination of topographical and histology codes based on ICD-O-3 were used. Incidence, demographics, tumor characteristics, and survival was then compared between these 2 histologic subtypes of pancreatic cancer. Results: A total of 57,688 patients with pancreatic cancer were identified, of which 53,753 (93%) had pancreatic adenocarcinoma and 3935 (7%) had PNET. The overall age-adjusted incidence of PNETs between 2004 and 2012 was 0.52 per 100,000 per year, whereas that for pancreatic adenocarcinomas during the same period was 7.34 per 100,000 per year. PNETs had a significantly younger median age at diagnosis (61 vs. 69 y). A significant proportion of PNETs were diagnosed at stage I (20.5% vs. 6.0%) and were well differentiated (32.8% vs. 4.5%) compared with adenocarcinomas. Five-year cause-specific survival was 51.3% and 5.0% for PNETs and pancreatic adenocarcinomas, respectively. In multivariate analysis, pancreatic adenocarcinomas had a hazard ratio for death of 4.02 (95% confidence interval, 3.79-4.28) when compared with PNETs. Conclusions: PNETs present with favorable features such as higher proportion of early-stage tumor, higher proportion of well differentiated tumors, and younger age at diagnosis. PNETs have a significantly better survival than pancreatic adenocarcinomas even after adjusting for age, sex, race, site, grade, and stage.

https://ift.tt/2HTN7mO

Locally Advanced Cervical Cancer: Outcomes With Variable Adherence to Treatment

Objective: Adherence to treatment regimen and schedule is recommended to improve control of disease and overall survival (OS) in locally advanced cervical cancer. However, treatment-related toxicities and patient and physician factors all impact timely completion of treatment. We sought to correlate adherence to treatment plan with survival and toxicities of patients treated for locally advanced cervical cancer. Materials and Methods: A retrospective review of patients treated for advanced cervical cancer at our institution between 2003 and 2011 was performed. Demographics, clinicopathologic variables, treatment, and disease outcomes were collected. Endpoints of disease outcome were disease-free survival and OS. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: A total of 162 patients met the inclusion criteria and were included in study analysis. A total of 95% of patients were treated with both radiation and concurrent chemotherapy. Mean radiation dose to point A was 72 Gy. In total, 77% had complete response to primary therapy. Severe (grade 3/4) late radiation toxicities were seen in 10.5% of patients. Stage and total radiation dose to point A were significant predictors of survival for the entire cohort. Among patients receiving at least 72 Gy and brachytherapy, duration of treatment was significantly associated with both disease-free survival and OS. Conclusions: Adherence to both optimal treatment time and radiation dose is significantly associated with improved survival. Total radiation dose is an independent predictor of survival among patients with locally advanced cervical cancer.

https://ift.tt/2F8tQLb

Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors

Objectives: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy. Methods: Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence. Results: Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8). Conclusions: Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

https://ift.tt/2HWlSb9

Utilization of Postoperative Chemoradiotherapy Among Women in the United States With High-risk Cervical Cancer

Objective: Prospective randomized data demonstrates that chemoradiotherapy (CRT) improves overall survival in women with high-risk pathologic features following radical hysterectomy. Despite this, not all high-risk patients receive adjuvant CRT and the patterns of care in this patient population are unknown. We sought to investigate the rates of adjuvant therapy utilization through analysis of the National Cancer Database. Materials and Methods: The National Cancer Database was queried for women with cervical cancer treated initially with hysterectomy from 2002 to 2012. Patients without high-risk pathologic features were excluded: pN+, positive surgical margins, and parametrial invasion (Peters' criteria). Among the 5947 evaluable patients, univariable analysis and multivariable analysis were performed to investigate potential factors associated with CRT utilization and overall survival following diagnosis. Results: Adjuvant CRT was performed in 41.8% of women and adjuvant radiotherapy, chemotherapy, and no adjuvant therapy was utilized in 9.8%, 23.6%, and 24.8% of women, respectively. On multivariable analysis, CRT utilization was associated with younger age, race, lower facility volume, pN+, parametrial invasion, and a negative surgical margin. Residence distance to treating facility, year of diagnosis, household income, insurance status, and facility type did not predict for CRT utilization. Conclusions: Despite level I evidence supporting its use, less than half of women in this large US cohort with high-risk cervical cancer received adjuvant CRT. Use of adjuvant CRT for women did not significantly increase between 2002 and 2012. Patient age, race, and pathologic risk factors were associated with use of adjuvant CRT.

https://ift.tt/2F8tQe9

Perioperative Mortality in Nonelderly Adult Patients With Cancer: A Population-based Study Evaluating Health Care Disparities in the United States According to Insurance Status

Objectives: The purpose of this study was to evaluate whether insurance status predicts for perioperative mortality (death within 30 d of cancer-directed surgery) for the 20 most common surgically treated cancers. Methods: The SEER database was examined for the 20 most common surgically resected cancers and included nonelderly adults, aged 18 to 64 years. The database was queried from 2007 to 2011, with a total of 506,722 patients included in the analysis. Results: Insurance status for all patients were the following: non-Medicaid insurance (83%), any Medicaid (10%), uninsured (4%), and unknown (3%). In univariate analyses, predictors for perioperative mortality included insurance status (P

https://ift.tt/2HTN6iK

Secondary Surgery Versus Chemotherapy for Recurrent Ovarian Cancer

Objective: The best course of treatment for recurrent ovarian cancer is uncertain. We sought to determine whether secondary cytoreductive surgery for first recurrence of ovarian cancer improves overall survival compared with other treatments. Materials and Methods: We assessed survival using Surveillance, Epidemiology and End Results-Medicare data for advanced stage ovarian cancer cases diagnosed from January 1, 1997 to December 31, 2007 with survival data through 2010 using multinomial propensity weighted finite mixture survival regression models to distinguish true from misclassified recurrences. Of 35,995 women ages 66 years and older with ovarian cancer, 3439 underwent optimal primary debulking surgery with 6 cycles of chemotherapy; 2038 experienced a remission. Results: One thousand six hundred thirty-five of 2038 (80%) women received treatment for recurrence of whom 72% were treated with chemotherapy only, 16% with surgery and chemotherapy and 12% received hospice care. Median survival of women treated with chemotherapy alone, surgery and chemotherapy, or hospice care was 4.1, 5.4, and 2.2 years, respectively (P

https://ift.tt/2Fe1wY8

Vulvar Recurrences After Intensity-modulated Radiation Therapy for Squamous Cell Carcinoma of the Anus

Objectives: The objective is to determine localregional control (LRC), distant metastasis free survival, disease-free survival, overall survival (OS), and toxicity for patients with squamous cell carcinoma of the anus treated with definitive chemotherapy and intensity-modulated radiation therapy (IMRT). Materials and Methods: We conducted a retrospective review of patients treated using IMRT for squamous cell carcinoma of the anus at our institution since 2005. Patients with local recurrences were identified and reviewed. The Kaplan-Meier curves were used for LRC and OS. Results: From 2005 to 2014, 52 patients were treated with IMRT-based chemoradiation for squamous cell carcinoma of the anus. Median dose to the primary tumor was 54 Gy. LRC, distant metastasis free survival, OS, and disease-free survival were 92.3%, 88.5%, 86.5%, and 84.6%, respectively, with a median follow-up of 20 months. Two local failures occurred at the anal primary site and 2 in the vulva. Despite subsequent palliative radiotherapy and chemotherapy, neither patient with a vulvar recurrence achieved disease control. Conclusions: In a cohort of patients treated with IMRT-based chemoradiation, 2 vulvar recurrences were identified within the avoided external genitalia despite limited recurrence rates within the cohort overall. This experience suggests that for patients with a locally advanced primary tumor and bulky bilateral inguinal or pelvic disease, the in-transit vulvar dermal lymphatics may be at risk for subclinical involvement and subsequent recurrence. If substantiated by a similar pattern of recurrence at other institutions, the external genitalia may need to be reclassified from an avoidance structure to a clinical treatment volume in patients with locally advanced anal cancer.

https://ift.tt/2HVMER8

Malignant Peripheral Nerve Sheath Tumors: A Single Institution’s Experience Using Combined Surgery and Radiation Therapy

Purpose: The purpose of this study is to investigate local control (LC), survival outcomes, and associated prognostic factors for patients with malignant peripheral nerve sheath tumors (MPNSTs) treated with combined surgery and radiation therapy (RT). Methods: We reviewed the medical records of 71 consecutive patients treated with surgery and RT for localized MPNST between 1965 and 2012. Preoperative RT was used to treat 23 patients (32%) to a median dose of 50 Gy (range, 50 to 60 Gy), whereas 48 (68%) received postoperative RT to a median dose of 64 Gy (range, 45 to 70 Gy). Results: Median follow-up for living patients was 118 months (range, 21 to 512 mo). The 5-year LC, distant metastatic free survival, and disease-specific survival rates were 84%, 62%, and 66%, respectively. To identify predictors of outcome, several multivariate models were constructed: (1) positive/uncertain surgical margin status was the only factor adversely associated local relapse at 5 years (28% vs. 5% for negative margins; P=0.02; hazard ratios 5.92; 95% confidence interval, 1.3-27.4). (2) No factors were significantly associated with distant metastatic free survival. Of the 35 patients (49%) who sustained disease relapse, only 3 were ultimately salvaged. Only 2 patients had grade 2 late toxicities (necrosis, fibrosis) based on Common Terminology Criteria for Adverse Events version 4.03 criteria, and 1 patient had grade 1 edema. Conclusions: Combination therapy with surgery and RT provides favorable LC. Distant recurrences, however, continue to be challenging with limited salvage success at the time of relapse.

https://ift.tt/2Fe1oYE

A Pooled Analysis of Biochemical Failure in Intermediate-risk Prostate Cancer Following Definitive Stereotactic Body Radiotherapy (SBRT) or High-Dose-Rate Brachytherapy (HDR-B) Monotherapy

Objectives: To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy. Materials and Methods: A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel χ2 metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure. Results: The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ≤3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS. Conclusions: With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.

https://ift.tt/2HRUYB7

Disparity in Outcomes for Adolescent and Young Adult Patients Diagnosed With Pediatric Solid Tumors Across 4 Decades

Objective: Cancer mortality is a leading cause of disease-related death in the adolescent and young adult (AYA) population. Compared with older and younger patients, AYA patients often experience worse cancer-specific outcomes. Here, we compare AYA and pediatric overall survival (OS) in the most common pediatric extracranial solid tumors. Materials and Methods: Using the US Surveillance, Epidemiology, and End Results database, we studied patients (age, 0 to 39 y) diagnosed with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma, and Wilms tumor. Results: A total of 12,375 patients (age, 0 to 39 y) were diagnosed between 1973 and 2010 (8247 pediatric and 4128 AYA patients). AYA patients with rhabdomyosarcoma and Ewing sarcoma were more likely to present with metastatic disease. OS was significantly worse in the AYA cohort for all tumor types (P

https://ift.tt/2FacFco

Impact of Staging With Positron-emission Tomography (PET) and Comorbidities on Management and Survival of American Veterans With Stage I-III Non–Small Cell Lung Cancer

Objectives: The extent of whether staging by fluorodeoxyglucose positron-emission tomography (PET) impacts outcomes in American Veterans with stage I-III non–small-cell lung cancer (NSCLC) is unknown. We investigated impact of fluorodeoxyglucose PET staging and age-adjusted comorbidities (AACs) on management and survival of NSCLC in this group. Materials and Methods: We performed a retrospective review to identify with NSCLC who underwent initial PET scan and received care at the Ann Arbor Veterans Hospital between 2005 and 2010. Survival outcomes were estimated by Kaplan-Meier methods, quantile regressions, and Cox proportional hazards models, after accounting for age at diagnosis, sex, AAC, and initial treatment. Results: The number of PET scans increased from 0 in 2005 to 66 in 2010. There were 170 men, 4 women, median age 64 years. Median AAC score was 4. In CS I (n=54), initial PET upstaged 5 patients. Median survival for no change in PET stage was 27.43 versus 67 months for upstaged patients (P=0.034). For CS II (n=15), initial PET scan upstaged 1 patient. Median survival for no change in PET stage was 16.53 versus 2.8 months for upstaged patient (P=0.335). For CS III (n=104), PET scan upstaged 20 patients. Median survival for no change in PET stage was 13.3 versus 3.8 months for upstaged patients (P=0.016). Conclusions: PET scans resulted in upstaging in 15% in CS I-III NSCLC. AAC scores dictated therapy decisions and outcomes more than PET staging. Veterans had lower 5-year survival rates (26.3%, 15.8%/13.4%) compared with 53% and 27% in age/sex/time-period matched SEER data for stage I-II/III NSCLC.

https://ift.tt/2HVbUa4

Erlotinib in routine clinical practice for first-line maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC)

Abstract

Purpose

The controlled phase III trial SATURN demonstrated that maintenance therapy with erlotinib after the first-line platinum-based chemotherapy prolonged progression-free survival (PFS) and overall survival (OS) of non-small cell lung cancer (NSCLC) patients with advanced, non-progressive disease. We conducted the non-interventional study SATURN NIS to investigate the effectiveness and tolerability of erlotinib maintenance in daily clinical practice.

Methods

This single-arm NIS screened 290 patients with locally advanced or metastatic NSCLC (stage IIIB or IV) and stable disease after standard platinum-based first-line chemotherapy in 95 institutions across Germany. Erlotinib was dosed and administered corresponding to the terms of the marketing authorization at the time of recruitment. The main effectiveness endpoint was subjects' OS at 1 year. Subgroup analyses of survival estimates of OS and PFS were performed.

Results

272 patients were eligible for analysis (median age 66 years, 37.1% females, 99.6% Caucasian, median ECOG performance status 1, 61.8% adenocarcinoma, 96.3% of patients with stable disease). Maintenance therapy with erlotinib resulted in median OS comparable to that of the SATURN phase III trial 10.4 months [95% CI: (8.8; 12.5) vs. 11.9 months]. The 1-year survival rate was 45.6% [95% CI: (37.5%; 53.6%)]. No new safety signals were observed. As expected, patients with epidermal growth factor receptor (EGFR) mutations derived a greater benefit concerning OS and PFS than EGFR–wild-type patients. Moreover, a significant association of OS and PFS and the smoking status was observed.

Conclusions

The results of this non-interventional study support the current clinical practice of erlotinib switch maintenance in EGFR-mutation-positive patients.

https://ift.tt/2K9rkZ1

Erlotinib in routine clinical practice for first-line maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC)

Abstract

Purpose

The controlled phase III trial SATURN demonstrated that maintenance therapy with erlotinib after the first-line platinum-based chemotherapy prolonged progression-free survival (PFS) and overall survival (OS) of non-small cell lung cancer (NSCLC) patients with advanced, non-progressive disease. We conducted the non-interventional study SATURN NIS to investigate the effectiveness and tolerability of erlotinib maintenance in daily clinical practice.

Methods

This single-arm NIS screened 290 patients with locally advanced or metastatic NSCLC (stage IIIB or IV) and stable disease after standard platinum-based first-line chemotherapy in 95 institutions across Germany. Erlotinib was dosed and administered corresponding to the terms of the marketing authorization at the time of recruitment. The main effectiveness endpoint was subjects' OS at 1 year. Subgroup analyses of survival estimates of OS and PFS were performed.

Results

272 patients were eligible for analysis (median age 66 years, 37.1% females, 99.6% Caucasian, median ECOG performance status 1, 61.8% adenocarcinoma, 96.3% of patients with stable disease). Maintenance therapy with erlotinib resulted in median OS comparable to that of the SATURN phase III trial 10.4 months [95% CI: (8.8; 12.5) vs. 11.9 months]. The 1-year survival rate was 45.6% [95% CI: (37.5%; 53.6%)]. No new safety signals were observed. As expected, patients with epidermal growth factor receptor (EGFR) mutations derived a greater benefit concerning OS and PFS than EGFR–wild-type patients. Moreover, a significant association of OS and PFS and the smoking status was observed.

Conclusions

The results of this non-interventional study support the current clinical practice of erlotinib switch maintenance in EGFR-mutation-positive patients.

from Cancer via ola Kala on Inoreader https://ift.tt/2K9rkZ1
via IFTTT

Pulmonary mass: never judge a book by its cover

Summary

Background

This case shows that a tumor can present in an uncommon way. When dealing with pulmonary masses, tissue remains the most important issue.

Clinical presentation

We present the case of a 71-year-old woman with a mass of more than 10 cm in the left lung. Pulmonary CT scan and PET scan confirmed this with also revealing mediastinal, thoracic and paravertebral invasion, without extrathoracic metastatic lesions. Bronchoscopic evaluation and ultrasound guided transbronchial needle aspiration could not yield a diagnosis. Because of rapid clinical deterioration, new imaging was performed, showing a cavitary lesion with air-fluid level in the tumor. Extensive microbiological work-up remained negative.

Intervention

To yield a pathological diagnosis, we performed a thoracotomy, revealing a polymorphic lymphoid infiltrate with scattered large atypical B-cells infected with Epstein-Barr virus, vasculitis and granulomatosis leading to a diagnosis of Lymphomatoid Granulomatosis. The patient received 6 cycles of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Methylprednisolone), 2 doses of Rituximab monotherapy, 4 doses of intrathecal Methotrexate and consolidation radiotherapy with a complete response.

Conclusion

Lymphomatoid granulomatosis (LYG) is a rare pulmonary disease, which should be included in the differential diagnosis of 'a pulmonary mass'. This case emphasizes the need for tissue acquisition.

https://ift.tt/2FaeqWM

Pulmonary mass: never judge a book by its cover

Summary

Background

This case shows that a tumor can present in an uncommon way. When dealing with pulmonary masses, tissue remains the most important issue.

Clinical presentation

We present the case of a 71-year-old woman with a mass of more than 10 cm in the left lung. Pulmonary CT scan and PET scan confirmed this with also revealing mediastinal, thoracic and paravertebral invasion, without extrathoracic metastatic lesions. Bronchoscopic evaluation and ultrasound guided transbronchial needle aspiration could not yield a diagnosis. Because of rapid clinical deterioration, new imaging was performed, showing a cavitary lesion with air-fluid level in the tumor. Extensive microbiological work-up remained negative.

Intervention

To yield a pathological diagnosis, we performed a thoracotomy, revealing a polymorphic lymphoid infiltrate with scattered large atypical B-cells infected with Epstein-Barr virus, vasculitis and granulomatosis leading to a diagnosis of Lymphomatoid Granulomatosis. The patient received 6 cycles of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Methylprednisolone), 2 doses of Rituximab monotherapy, 4 doses of intrathecal Methotrexate and consolidation radiotherapy with a complete response.

Conclusion

Lymphomatoid granulomatosis (LYG) is a rare pulmonary disease, which should be included in the differential diagnosis of 'a pulmonary mass'. This case emphasizes the need for tissue acquisition.

from Cancer via ola Kala on Inoreader https://ift.tt/2FaeqWM
via IFTTT

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report

Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and g...

https://ift.tt/2HMdqOg

Acetylshikonin attenuates angiotensin II-induced proliferation and motility of human brain smooth muscle cells by inhibiting Wnt/β-catenin signaling

Abstract

Cerebrovascular smooth muscle cell proliferation and migration contribute to hyperplasia in case of cerebrovascular remodeling and stroke. In the present study, we investigated the effects of acetylshikonin, the main ingredient of a Chinese traditional medicine Zicao, on human brain vascular smooth muscle cell (HBVSMCs) proliferation and migration induced by angiotensin II (AngII), and the underlying mechanisms. We found that acetylshikonin treatment significantly inhibited AngII-induced HBVSMCs proliferation and cell cycle transition from G1 to S phase. Wound-healing assay and Transwell assay showed that AngII-induced cell migration and invasion were markedly attenuated by acetylshikonin. In addition, AngII challenge significantly induced Wnt/β-catenin signaling activation, as evidenced by increased β-catenin phosphorylation and nuclear translocation and GSK-3β phosphorylation. However, acetylshikonin treatment inhibited the activation of Wnt/β-catenin signaling. Consequently, western blotting analysis revealed that acetylshikonin effectively reduced the expression of downstream target genes in AngII-treated cells, including c-myc, survivin and cyclin D1, which contributed to the inhibitory effect of acetylshikonin on HBVSMCs proliferation. Further, stimulation with recombinant Wnt3a dramatically reversed acetylshikonin-mediated inhibition of proliferation and cell cycle transition in HBVSMCs. Our study demonstrates that acetylshikonin prevents AngII-induced cerebrovascular smooth muscle cells proliferation and migration through inhibition of Wnt/β-catenin pathway, indicating that acetylshikonin may present a potential option for the treatment of cerebrovascular remodeling.

from Cancer via ola Kala on Inoreader https://ift.tt/2HloWN2
via IFTTT

Acetylshikonin attenuates angiotensin II-induced proliferation and motility of human brain smooth muscle cells by inhibiting Wnt/β-catenin signaling

Abstract

Cerebrovascular smooth muscle cell proliferation and migration contribute to hyperplasia in case of cerebrovascular remodeling and stroke. In the present study, we investigated the effects of acetylshikonin, the main ingredient of a Chinese traditional medicine Zicao, on human brain vascular smooth muscle cell (HBVSMCs) proliferation and migration induced by angiotensin II (AngII), and the underlying mechanisms. We found that acetylshikonin treatment significantly inhibited AngII-induced HBVSMCs proliferation and cell cycle transition from G1 to S phase. Wound-healing assay and Transwell assay showed that AngII-induced cell migration and invasion were markedly attenuated by acetylshikonin. In addition, AngII challenge significantly induced Wnt/β-catenin signaling activation, as evidenced by increased β-catenin phosphorylation and nuclear translocation and GSK-3β phosphorylation. However, acetylshikonin treatment inhibited the activation of Wnt/β-catenin signaling. Consequently, western blotting analysis revealed that acetylshikonin effectively reduced the expression of downstream target genes in AngII-treated cells, including c-myc, survivin and cyclin D1, which contributed to the inhibitory effect of acetylshikonin on HBVSMCs proliferation. Further, stimulation with recombinant Wnt3a dramatically reversed acetylshikonin-mediated inhibition of proliferation and cell cycle transition in HBVSMCs. Our study demonstrates that acetylshikonin prevents AngII-induced cerebrovascular smooth muscle cells proliferation and migration through inhibition of Wnt/β-catenin pathway, indicating that acetylshikonin may present a potential option for the treatment of cerebrovascular remodeling.

https://ift.tt/2HloWN2