Treatment algorithm and prognostic factors for patients with stage I-III carcinoma of the anal canal: a 20-year multicenter study.

Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.

Salvage extended field or involved field nodal irradiation in 18F-fluorocholine PET/CT oligorecurrent nodal failures from prostate cancer.

PURPOSE: The concept of metastasis-directed therapy for nodal oligorecurrences with stereotactic body radiotherapy is increasingly accepted. Hence, the comparison between salvage extended field radiotherapy (s-EFRT) and salvage involved field radiotherapy (s-IFRT) in patients with 18F-fluorocholine (FCH) PET/CT+ nodal oligorecurrences from prostate cancer is worthy of investigation. METHODS: Patients with oligorecurrent nodes on FCH PET/CT treated with salvage radiotherapy between 2009 and 2017 in a single tertiary cancer centre were selected for this study. Patients treated with s-IFRT were compared with those treated with s-EFRT. Toxicities and times to failure (TTF) were compared between the two groups. RESULTS: The study included 62 patients with positive lymph nodes only who underwent FCH PET/CT for a rising PSA level after radical prostatectomy or radiotherapy. Of these patients, 35 had s-IFRT and 27 had s-EFRT. After a median follow-up of 41.8 months (range 5.9-108.1 months), no differences were observed in acute or late gastrointestinal and genitourinary toxicities of grade 2 or more between the two groups. The 3-year failure rates were 55.3% (95% CI 37.0-70.3%) in the s-IFRT group and 88.3% (95% CI 66.9-96.1%) in the s-EFRT group (p = 0.0094). In multivariate analysis of TTF, an interval of >5 years was significantly correlated with better outcomes (HR = 0.33, 95% CI 0.13-0.86, p = 0.023). There was a strong trend toward better outcomes with s-EFRT even after adjusting for concomitant androgen-deprivation therapy (HR = 0.38, 95% CI 0.12-1.27, p = 0.116). CONCLUSION: FCH PET-positive node-targeted s-EFRT is feasible with low rates of toxicity and longer TTF, suggesting that oligorecurrent nodal disease diagnosed on FCH PET is unlikely.

Randomized phase II trial in prostate cancer with hormone-sensitive OligometaSTatic relapse: Combining stereotactic ablative radiotherapy and durvalumab (POSTCARD GETUG P13): Study protocol.

Background: As in other solid tumors, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis than patients with extensive metastatic disease. Stereotactic body radiotherapy (SBRT) is now considered an option in this population.Programmed death-1 (PD-1) and its ligands (PD-L1) are targeted by immune checkpoint inhibitors. Preclinical studies have shown that the tumor immune microenvironment changes when combining radiotherapy with immunotherapy, especially with hypofractionated radiotherapy.The oligometastatic setting appears to be the most relevant clinical situation for evaluating the immune response generated by radiotherapy and immune checkpoint inhibitors in patients with an intact immune system.We hypothesize that durvalumab will enhance the immune response following SBRT targeting oligometastatic lesions. Our purpose is to demonstrate, via a randomized 2:1 phase II trial, that SBRT (3 fractions) with durvalumab in oligometastatic hormone-sensitive prostate cancer patients would improve progression-free survival in patients with prostate cancer with up to 5 metastases compared to patients who exclusively received SBRT. Methods: This is a multicentric randomized phase II study in French academic hospitals. Patients with prostate cancer and up to 5 metastases (lymph node and/or bone) were randomized into a 2:1 ratio between Arm A (experimental group), corresponding to durvalumab and SBRT to the metastases, and Arm B (control group), corresponding to SBRT alone to the metastases. The study aims to accrue a total of 96 patients within 3 years. The primary endpoint is two-year progression-free survival and secondary endpoints include androgen deprivation therapy-free survival, quality of life, toxicity, prostate cancer specific survival, overall survival, and immune response. Discussion: The expected benefit for the patients in the experimental arm is longer life expectancy with acceptable toxicity. We also expect our study to provide data for better understanding the synergy between immunotherapy and radiotherapy in oligometastatic prostate cancer.

An Anal Lesion in a 27-Year-Old Patient.

A 27-year-old male patient presented with anal discomfort and pruritus for 3 months. What is your diagnosis?

Comparing simultaneous integrated boost vs sequential boost in anal cancer patients: results of a retrospective observational study.

BACKGROUND: To evaluate clinical outcomes of simultaneous integrated boost (SIB) - intensity modulated radiotherapy (RT) in patients with non metastatic anal cancer compared to those of a set of patients treated with 3-dimensional conformal RT and sequential boost (SeqB). METHODS: A retrospective cohort of 190 anal cancer patients treated at 3 academic centers with concurrent chemo-RT employing either SIB or SeqB was analysed. The SIB-group consisted of 87 patients, treated with 2 cycles of Mitomycin (MMC) and 5-Fluorouracil (5FU) using SIB-IMRT delivering 42-45Gy/28-30 fractions to the elective pelvic lymph nodes and 50.4-54Gy/28-30fractions to the primary tumor and involved nodes, based on pre-treatment staging. The SeqB group comprised 103 patients, treated with MMC associated to either 5FU or Capecitabine concurrent to RT with 36 Gy/20 fractions to a single volume including gross tumor, clinical nodes and elective nodal volumes and a SeqB to primary tumor and involved nodes of 23.4 Gy/13 fractions. We compared colostomy-free survival (CFS), overall survival (OS) and the cumulative incidence of colostomy for each radiation modality. Cox proportional-hazards model addressed factors influencing OS and CFS. RESULTS: Median follow up was 34 (range 9-102) and 31 months (range 2-101) in the SIB and SeqB groups. The 1- and 2-year cumulative incidences of colostomy were 8.2% (95%CI:3.6-15.2) and 15.0% (95%CI:8.1-23.9) in the SIB group and 13.9% (95%CI: 7.8-21.8) and 18.1% (95%CI:10.8-27.0) in the SeqB group. Two-year CFS and OS were 78.1% (95%CI:67.0-85.8) and 87.5% (95%CI:77.3-93.3) in the SIB group and 73.5% (95%CI:62.6-81.7) and 85.4% (95%CI:75.5-91.6) in the SeqB, respectively. A Cox proportional hazards regression model highlighted an adjusted hazard ratio (AdjHR) of 1.18 (95%CI: 0.67-2.09;p = 0.560), although AdjHR for the first 24 months was 0.95 (95%CI: 0.49-1.84;p = 0.877) for the SIB approach. CONCLUSIONS: SIB-based RT provides similar clinical outcomes compared to SeqB-based in the treatment of patients affected with non metastatic anal cancer.

Evaluation of a 36 Gy elective node irradiation dose in anal cancer.

PURPOSE: To retrospectively analyze the efficacy of 36 Gy of elective node irradiation and report patterns of recurrence in patients with anal cancer treated by chemoradiation with the same radiotherapy (RT) treatment scheme. METHODS AND MATERIALS: Between January 1996 and December 2013, 142 patients with anal squamous cell cancer were scheduled to receive a dose of 36 Gy of elective node irradiation (ENI) to the inguinal area and whole pelvis over 4 weeks followed after a 2-week gap by a boost dose of 23.4 Gy over 17 days to the macroscopic disease. Mitomycin C combined with fluorouracil, capecitabin or cisplatin was given at day 1 of each sequence of RT. RESULTS: Disease stages were I: 3, II: 78, IIIA: 23, IIIB: 38. Compliance rates were 97.2% with RT and 87.9% with chemotherapy. After a median follow up of 48 months [3.6-192], estimated 5-year overall survival and colostomy-free survival were 75.4% and 85.3% respectively. Eleven patients (7.7%) never achieved a complete response, 15 had a local component of recurrence and 5 a regional one. One patient had failure in the common iliac node area outside the treatment fields. The inguinal control rate was 98.5%. The 5-year tumor and nodal control rates were 81.5% and 96.0%, respectively. CONCLUSION: Chemoradiation with a dose of 36 Gy ENI achieved excellent nodal control. However, it is necessary to improve the 5-year control rate of the primary tumor. Omitting the gap and using additional doses per fraction or hyper-fractionation are to be explored.

Pattern of occult nodal relapse diagnosed with (18)F-fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy.

INTRODUCTION: The purpose of this study was to describe the pattern of nodal relapse with (18)F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. MATERIALS AND METHODS: Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTVRTOG). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. RESULTS: Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had ⩾2 positive nodes on FCH PET/CT (OR=8.75, [95% CI: 1.38-54.80], p=0.020). Relapses that occurred outside the CTVRTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. CONCLUSION: 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse.