Acute toxicity grade 3 and 4 after irradiation in children and adolescents: results from the IPPARCA collaboration

Publication date: Available online 19 December 2015
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Caroline Pixberg, Raphael Koch, Hans-Theodor Eich, Ulla Martinsson, Ingrid Kristensen, Christiane Matuschek, Rolf-Dieter Kortmann, Fabian Pohl, Khaled Elsayad, Hans Christiansen, Normann Willich, Jack Lindh, Diana Steinmann
Background and PurposeIn the context of oncologic therapy for children, radiotherapy is frequently indicated. The aim of this study was to identify the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae.Patients and MethodsIrradiated children have been prospectively documented since 2001 in the RiSK-registry in Germany and since 2008 in the RADTOX-registry in Sweden. Data were collected using standardized, previously published forms. Toxicity classification was based on the criteria of RTOG/EORTC.ResultsAs of June 2013, 1500 children had been recruited into the RiSK-database and 485 into the RADTOX-registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grade 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24) and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) compared to patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, a diagnosis of Ewing sarcoma and total radiation dose showed a statistically noticeable effect (p≤0.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, acute toxicity influenced the time until maximal late toxicity.ConclusionIn general high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.

Teaser

In the context of radiotherapy at children the aim of this study is to identify the frequency and reasons of the development of a high grade acute toxicity as well as possible sequelae. For this purpose prospectively documented data of irradiated children is evaluated whereby for the first time data of two international projects is combined ("Risk" and "IPPARCA"). From this we gain better inside into the side effects of radiotherapy.


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Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or HIFU

Publication date: Available online 19 December 2015
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Adam L. Holtzman, Bradford S. Hoppe, Haley P. Letter, Romaine C. Nichols, Randal H. Henderson, William M. Mendenhall, Christopher G. Morris, Christopher R. Williams, Zuofeng Li, Nancy P. Mendenhall
PurposeLocal recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. The purpose of this paper is to review a single institution's experience in using PT for salvage of local recurrent disease after HIFU or CS.Methods and MaterialsWe reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(RBE) (range, 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy (ADT) with RT. Patients were evaluated for quality of life (QOL) using the EPIC questionnaire and toxicity using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually.ResultsMedian follow-up was 37 months (range, 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year PT-related grade 3 toxicity rates was 17%. At 1 year, bowel summary, urinary incontinence and urinary obstructive quality of life (QOL) scores declined, but only the bowel QOL score at 12 months met the minimally important difference MID threshold.ConclusionPT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT function. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

Teaser

Local recurrence of prostate cancer after cryosurgery (CS) or high-intensity focused ultrasound (HIFU) is an emerging problem as these treatments are increasingly offered in lieu of standard radiation therapy and surgery. In this small study, salvage proton therapy (PT) achieved a high rate of bPFS with acceptable toxicity and minimal changes in the IPSS and EPIC summary scores compared with baseline pre-PT function.


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A prospective study of measured body size and height and risk of keratinocyte cancers and melanoma

Publication date: February 2016
Source:Cancer Epidemiology, Volume 40
Author(s): Petra H. Lahmann, Maria Celia B. Hughes, Gail M. Williams, Adèle C. Green
BackgroundThe potential influence of measured body weight and height on keratinocyte skin cancer risk has scarcely been studied. Some evidence indicates melanoma risk increases as self-reported height increases, but an association with body mass index (BMI) is less certain.MethodsWe measured body weight and height of 1171 Australian men and women in a community-based skin cancer study in Queensland and prospectively examined the association of BMI, body surface area (BSA) and height and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma while accounting for skin phenotype, sun exposure, clinical/cutaneous signs of chronic photodamage and other risk factors.ResultsDuring 16 years of follow-up, 334 and 188 participants newly developed BCC and SCC, respectively; 28 participants were diagnosed with primary melanoma. BMI and BSA were unrelated to skin cancer incidence. After full adjustment, height was significantly associated with SCC development in men (relative risk (RR)=1.66; 95% confidence interval (CI)=1.11–2.48, for ≥175cm vs ≤171cm, Ptrend=0.017), and BCC in women (Ptrend=0.043). Melanoma in men, was similarly positively associated with height (RR per 5cm increment=1.55; 95%CI 0.97–2.47, P=0.067) though not significantly.ConclusionThis study shows that after adjusting for sun exposure tall stature may be a risk factor for the most common types of skin cancer BCC, SCC, and melanoma, while body mass and surface area appear unrelated to risk.



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Is the irradiated small bowel volume still a predictor for acute lower gastrointestinal toxicity during preoperative concurrent chemo-radiotherapy for rectal cancer when using intensity-modulated radiation therapy?

The small bowel (SB) represents the most important dose-limiting structure in pelvic radiotherapy (RT). However, we observed that the majority of rectal cancer patients who received preoperative pelvic intensi...

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Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma: A Nordic Multicenter Comparative Study

Abstract

Background

This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery is uncertain.

Methods

Data from patients with a diagnosis of hgPNEC determined between 1998 and 2012 were retrospectively registered at 10 Nordic university hospitals. Kaplan–Meier curves were used to compare the overall survival of different treatment groups, and Cox-regression analysis was used to evaluate factors potentially influencing survival.

Results

The study registered 119 patients. The median survival period from the time of metastasis was 23 months for patients undergoing initial resection of localized nonmetastatic disease and chemotherapy at the time of recurrence (n = 14), 29 months for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor and metastatic disease was 69 %. Resection of the primary tumor was an independent factor for improved survival after occurrence of metastatic disease.

Conclusions

Patients with resected localized nonmetastatic hgPNEC and later metastatic disease seemed to benefit from initial resection of the primary tumor. Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment.

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Impact of Time from Completion of Neoadjuvant Chemotherapy to Surgery on Survival Outcomes in Breast Cancer Patients

Abstract

Background

No studies have examined the impact of the interval from conclusion of neoadjuvant chemotherapy to surgery in breast cancer patients. This study was undertaken to investigate the relationship between time interval from neoadjuvant chemotherapy to surgery and survival outcomes.

Methods

Breast cancer patients diagnosed with stage I–III disease who received neoadjuvant chemotherapy June 1995 to April 2007 were identified. The effect of neoadjuvant chemotherapy to surgery interval, defined as ≤4, 4–6, or >6 weeks, on survival outcomes was examined. Descriptive statistics and Cox proportional hazards models were used.

Results

A total of 1101 patients were identified. Median time to surgery was 33 (range 8–159) days; 335 patients (30.4 %) had surgery within 4 weeks of their last dose of neoadjuvant chemotherapy, 524 (47.6 %) within 4–6 weeks, and 242 (22.0 %) after more than 6 weeks. Median follow-up was 94 (range 3–178) months. The 5-year overall survival (OS) estimates were 79, 87, and 81 % in patients who underwent surgery ≤4, 4–6, and >6 weeks after neoadjuvant chemotherapy, respectively (p = 0.03). The three groups did not differ in 5-year recurrence-free survival (RFS) or locoregional recurrence-free survival (LRFS). In multivariable analysis, compared with an interval of ≤4 weeks, patients who underwent surgery at 4–6 or >6 weeks had equivalent OS, LRFS, and RFS; a sensitivity analysis suggested worse OS in patients who underwent surgery at >8 weeks.

Conclusions

Patients with neoadjuvant chemotherapy to surgery intervals of up to 8 weeks had equivalent OS, RFS, and LRFS.

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Characterization of the expression of the pro-metastatic Mena INV isoform during breast tumor progression

Abstract

Several functionally distinct isoforms of the actin regulatory Mena are produced by alternative splicing during tumor progression. Forced expression of the Mena^INV isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed Mena^INV within primary tumors during progression remain unknown, as most studies to date have only assessed relative mRNA levels from dissociated tumor samples. We have developed a Mena^INV isoform-specific monoclonal antibody and used it to examine Mena^INV expression patterns in mouse mammary and human breast tumors. Mena^INV expression increases during tumor progression and to examine the relationship between Mena^INV expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while Mena^INV robustly expressed in vascularized areas of the tumor, it is not confined to cells adjacent to blood vessels. Altogether, these data demonstrate the specificity and utility of the anti-Mena^INV-isoform specific antibody, and provide the first description of endogenous Mena^INV protein expression in mouse and human tumors.

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