Nodal Elective Volume Selection and Definition during Radiation Therapy for Early Stage (T1-T2 N0 M0) Perianal Squamous Cell Carcinoma: A Narrative Clinical Review and Critical Appraisal.

Distinction between anal canal and perianal squamous cell carcinomas (pSCCs) is essential, as these two subgroups have different anatomical, histological, and lymphatic drainage features. Early-stage true perianal tumors are very uncommon and have been rarely included in clinical trials. Perianal skin cancers and aCCs are included in the same tumor classification, even though they have different lymphatic drainage features. Furthermore, pSCCs are treated similarly to carcinomas originating from the anal canal. Radiation therapy (RT) is an essential treatment for anal canal tumors. Guidelines do not differentiate between treatment volumes for perianal tumors and anal cancers. So far, in pSCC, no study has considered modulating treatment volume selection according to the stage of the disease. We conducted a narrative literature review to describe the sites at higher risk for microscopic disease in patients with early-stage perianal cancers (T1-T2 N0 M0) to propose a well-thought selection of RT elective volumes.

Dose prescription in SBRT for early-stage non-small cell lung cancer: are we all speaking the same language?

INTRODUCTION: Stereotactic body radiation therapy is increasingly used in the treatment of early-stage lung cancers. Guidelines provide indications regarding the constraints to the organs at risk (OARs) and the minimum coverage of the planning target volume but do not suggest optimal dose distribution. Data on dose distribution from the different published series are not comparable due to different prescription modalities and reported dose parameters. METHODS: We conducted a review of the published data on dose prescription, focusing on the role of homogeneity on local tumor control, and present suggestions on how to specify and report the prescriptions to permit comparisons between studies or between cases from different centers. CONCLUSIONS: To identify the dose-prescription modality that better correlates with oncologic outcomes, future studies should guarantee a close uniformity of dose distribution between cases and complete dose parameters reporting for treatment volumes and OARs.

Predictive value of Prostate Specific Antigen variations in the last week of salvage radiotherapy for biochemical recurrence of prostate cancer after surgery: A practical approach.

BACKGROUND: About a third of patients who underwent radical prostatectomy for prostate cancer (Pca) develop a biochemical failure (BF) within 10 years from surgery, and about a half of them receive salvage radiation therapy (SRT). Factors to predict risk to relapse after SRT are still lacking. Dynamic models, based on the assessment of changes in Prostate Specific Antigen (PSA) postsurgery seem to show good reliability. AIMS: The goal of the study was to identify a simple analytical method for the postsalvage radiation therapy biochemical failure (post-SRTBF) prediction before the end of the SRT, regardless of the PSA value at the beginning of the treatment (PSA start), measuring the PSA values at the start and 1 week before the end of SRT. METHODS: In a series of 83 patients treated with SRT for BF of Pca we measured PSA values at the first day and 1 week before the end of SRT. These values were used to define an analytical method for the post-SRTBF prediction. RESULTS: PSA value in patients without post-SRTBF show a significant difference in term of difference during the SRT with respect to patients with post-SRTBF. Starting from this difference, we identified a simple and practical analytical method for the post-SRTBF prediction before the end of the SRT. The data corresponds with the model and the analytical method is highly predictive (Sensitivity = 81%, Specificity = 85%, Accuracy = 83%). CONCLUSION: This study offers a new tool to early predict Pca relapse overtime and to select patients who can benefit from an early additional systemic treatment.

Reoxygenation Reverses Hypoxia-related Radioresistance in Head and Neck Cancer Cell Lines.

BACKGROUND/AIM: Head and neck cancer (HNC) is characterized by epidermal growth factor receptor (EGFR) overexpression and radiotherapy (RT) resistance. Cancer cells are able to survive and proliferate in hypoxic conditions. Hypoxia can be transiently interrupted by phases of reoxygenation. This work aimed to analyze the reoxygenation effect on proliferation in response to radiation in HNC cells. MATERIALS AND METHODS: HNC cell lines CAL33 and CAL166 were subjected to an 8-Gy radiation dose in hypoxia and/or after reoxygenation. Cell proliferation and molecular factors involved in response to treatments were studied. RESULTS: Cytotoxicity test confirmed radioresistance in hypoxia and highlighted that reoxygenation before RT restores sensitivity in both cell lines. Our results showed a similar proliferation inhibition effect and EGFR modulation but a different cell death mechanism in the two cell lines after treatment. CONCLUSION: Reoxygenation before RT rescued radiosensitivity in HNC cells.

Facial Basal Cell Carcinomas in Elderly Frail Patients Treated with Low Total-dose Radiotherapy.

AIM: A retrospective analysis was performed in our two Institutions in order to evaluate the feasibility and reliability of a hypofractionated-radiotherapy regimen in the treatment of frail elderly patients with facial basal cell carcinomas (BCCs). PATIENTS AND METHODS: The records of elderly patients (age >75 years) with histologically-confirmed BCC, T1-2, treated to a total radiation dose of 25-30 Gy over 5-6 weeks, were retrospectively analyzed. RESULTS: From February 2007-December 2010, 134 ambulatory patients with 159 BCCs were treated. Their median age was 82.5 years (range=75-103). Grade 1-2 skin acute toxicities were observed in 30.6% of patients (41/134). Complete responses were observed in 157 tumors in 132 patients. At the last follow-up, June 2014, no late toxicities had been noted; three patients had local recurrent disease. CONCLUSION: Our results seem to demonstrate both the feasibility and efficacy of curative hypofractionated radiation therapy in elderly patients with BCCs unfit for daily irradiation.

Reliability of prostate-specific antigen-marker in determining biochemical failure during the first 2 years after external beam radiation therapy and hormone therapy in patients with non-operated prostate cancer.

OBJECTIVES: The presence of prostate-specific antigen (PSA)-bounce after external beam radiation therapy (EBRT) and hormone therapy (HT) makes PSA an unreliable marker in determining PSA biochemical failure (PSA-BF) during the first 2 years after EBRT + HT in patients with non-operated prostate cancer (CaP). To determine the reliability of PSA-BF in predicting clinical outcomes, the Kamat definition, which does not consider PSA-BF during the first 24 months after EBRT, was tested against three other more frequently used methods (American Society of Radiation Oncology, Vancouver, and American Society of Radiation Oncology-Phoenix), which do. Secondly, their relative accuracies in predicting the clinical outcomes were also calculated. MATERIALS AND METHODS: In January 2011, 193 consecutive CaPs, treated with radical EBRT + HT in our institution from 1999 to 2002, were retrospectively investigated. BF was calculated according to the Kamat definition against the other three above-mentioned methods. Each BF-free survival was analyzed in function of every clinical endpoint (clinical-failure-free survival, cause specific survival, and overall survival) using univariate and multivariate Cox regression analyses. The accuracy of each definition in predicting clinical relapse was also calculated and compared. RESULTS: Only the Kamat BF definition had both a significant Cox hazard ratio, regarding clinical events or cancer deaths, and the best accuracy values in predicting clinical outcomes. Retrospective study design was the major limitation of the study. CONCLUSIONS: Only the Kamat definition, which does not consider PSA-BF during the first 24 months after EBRT + HT, was shown to be a reliable predictor of clinical events. Thus, our results suggest that solely PSA-based BF should not be considered as a reliable surrogate endpoint during the first 24 months after EBRT + HT. Consequently, caution should be used in adopting rescue treatment without further work-up on an individual basis.

Role of IL-8 induced angiogenesis in uveal melanoma.

Introduction Uveal melanoma (UM) is a highly vascularised tumour generally treated with radiotherapy (RT). A recent preclinical study from our group [1] demonstrated that RT-associated anti-angiogenic therapy has more than additive effects on cell growth, by modulating vascular endothelial growth factor (VEGF) levels. The pro-angiogenic interleukin-8 (IL-8) is highly expressed in both tumour and endothelial cells and is associated with resistance to VEGF-targeted therapies in various tumour types. The aim of this study is to investigate IL-8 release in response to the anti-angiogenic drug bevacizumab (AV) and RT given alone and in combination. Material and methods The human ocular melanoma cells (OCM-1) and human umbilical vein endothelial cells (HUVEC) were grown in transwell plates. AV was administered at a 2,500 µg/ml dose and cells were irradiated with a 6 Gy dose. IL-8 concentrations were determined by ELISA assay. Protein expression was detected by western blot. Results AV alone or in combination with RT reduces VEGF levels in both cell lines when co-cultured; unexpectedly, RT alone did not increase VEGF levels. In transwell plate AV alone lowered IL-8 secretion in both cell lines. This inhibitory effect was reduced when co-cultured cells are treated with AV + RT, suggesting that RT-induced VEGF may reactivate IL-8 secretion, enhancing an alternative pathway to sustain tumour angiogenesis. Conclusions These data indicate that the UM microenvironment, beside VEGF, can activate IL-8 signalling as an alternative pro-angiogenic pathway.

Concomitant chemotherapy and external radiotherapy plus brachytherapy for locally advanced esophageal cancer: results of a retrospective multicenter study.

AIMS AND BACKGROUND: In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable. METHODS AND STUDY DESIGN: Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients. RESULTS: At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pT0) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy. CONCLUSIONS: For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.