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Background Primary cutaneous marginal zone B-cell lymphoma ( PCMZL) has rarely been reported in patients younger than 20 years. Objectives To report our experience with PCMZL in the paediatric/adolescent age group. Methods Medical records of patients diagnosed with PCMZL before age 20 years and managed at two cutaneous lymphoma clinics in the U.S.A. and Israel from 1992 to 2015 were reviewed. Results The study group included 11 patients (six girls; median age 16 years, range 6-19·5); 10 had generalized/multifocal (T3) and one had regional/localized (T2) disease. Lesions were located on the limbs in all patients and the trunk in six; two had facial lesions. Staging in all but one was based on whole-body computed tomography or positron emission tomography. Initial management in most patients included nonradiation modalities: one patient with localized disease received intralesional steroids; six patients with multifocal disease received the following: topical/intralesional steroids ( n = 3); excision ( n = 2); 'watch and wait' ( n = 1). No extracutaneous progression was noted during a median follow-up of 5·5 years (mean 7·5, range 0·5-14). At present, five patients are in complete remission. Conclusions Based on our data (largest series in the literature with the longest follow-up), the clinicopathological presentation and course of PCMZL in the paediatric/adolescent age group are similar to those in adults. Given the indolent course and the long life expectancy of these young patients, the cumulative risk of imaging studies and the age-related potential toxicity of treatment, especially radiation, should be taken into consideration. [ABSTRACT FROM AUTHOR]

Background: Unilesional folliculotropic mycosis fungoides (UFMF) has been rarely reported. Objective: The aim of this study was to describe our experience with UFMF. Methods: Data were collected on all patients with clinicopathological UFMF who attended the Department of Dermatology of a tertiary university-affiliated medical centre in 1996-2013 and were followed prospectively. Results: The sample included seven patients (five male, two female) of mean age 38 years at diagnosis; two were aged <18 years. The lesion presented as a solitary patch/plaque with follicular accentuation in five patients, an infiltrated plaque devoid of hair in one and with follicular nodules in one. Four patients had alopecia, and one, secondary anetoderma. The lesion was located on a limb in four patients, the trunk in two, and the face in one. In all cases, the atypical folliculotropic lymphocytes expressed mainly surface CD4+. Monoclonality was detected in three of the six patients analysed. Treatment consisted of localized electron beam in five patients, all of whom had a complete response (CR), and excision in one patient. The remaining patient, a 9-year-old boy, was treated with topical psoralen and UVA with CR. The duration of follow-up was 0.5-10 years (mean 4). There were no recurrences in six patients and local recurrence in one. Conclusion: UFMF presents at a young age, usually with early disease clinical morphology. The treatment goal should be cure. Our experience indicates an excellent prognosis of early UFMF with no multifocal/internal spread. [ABSTRACT FROM AUTHOR]

Study Objectives: High dose rate (HDR) endobronchial brachytherapy is widely used as a palliative treatment for symptomatic airway obstruction by primary or secondary malignant tumors. We report on a successful use of HDR brachytherapy in patients with nonmalignant airway obstruction.Design: Case seriesPatients: Six patients received HDR brachytherapy for airway obstruction caused by granulation tissue around a metal stent placed for restoration of the airway patency for nonmalignant causes. In four patients, brachytherapy was performed following recurrent occlusion of the airway by granulation tissue formation; in two patients, it was done as a prophylactic procedure.Intervention: HDR brachytherapy catheters were passed through the metal stents under direct fluoroscopic guidance. Simulation and computerized treatment planning were done, and a single dose of 10 Gy was administered using a brachytherapy remote afterloader with a (192)Ir source. The dose was prescribed to a distance of 1 cm from the center of the source, with a margin of 1 cm from the proximal and distal ends of the stent.Results: At a median follow-up of 15 months, moderate granulation tissue formation was observed in only one patient; in four others, it was categorized as minimal, 5 to 30 months from the procedure. Restoration of the lumen was complete in four patients, near complete in one patient, and partial in one patient. In one patient, previously treated by external radiotherapy, local tissue necrosis was evident.Conclusion: HDR brachytherapy can be used safely for nonmalignant airway obstruction. Further studies including more patients and longer follow-up are needed. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative chemoradiation as per Intergroup-0116 trial ("Macdonald regimen") is considered standard for completely resected high risk gastric cancer. However, many concerns remain with regards to the toxicity of this regimen. To evaluate the safety and tolerability of this regimen in a routine clinical practice setting, we analyzed our experience with its use. As we did not expect a different toxic profile in patients (pts) with positive margins (R1 resection), these were studied together with pts after complete resection (R0). Patients and Methods Postoperative chemoradiation therapy was given according to the original Intergroup-0116 regimen. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of OS and DFS between R0 and R1 pts was done using the log-rank test. Results Between 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection of locally advanced gastric adenocarcinoma received postoperative chemoradiation; 61% were male and the median age was 63 years (range, 23-86); 78% had T ≥ 3 tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54% completed the entire chemoradiation plan; 46.4% had grade ≥ 3 toxicity and 32% were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity: diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small bowel gangrene (1). The most common hematological toxicity was neutropenia, grade ≥ 3 in 30% of pts and complicated by fever in 15%. The most common non-hematological toxicities were nausea, vomiting and diarrhea. With a median follow-up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are free of disease. Median DFS and OS for R0 were not reached. R0 pts had a significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p = 0.01) compared with R1 pts. Conclusions In our experience, postoperative chemoradiation as per Intergroup-0116 seems to be substantially toxic, with a mortality rate which seems higher than reported in that trial. Efficacy data appears comparable to the original report. Following postoperative chemoradiation, involvement of surgical margins still has a detrimental impact on patient outcome.

Background: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, affecting predominantly the fair-skinned older population exposed to high levels of ultraviolet light. Immune suppression is considered a significant risk factor. With the recent advances in the field of immunotherapy, the treatment paradigm for advanced MCC, traditionally based on chemotherapy, has largely shifted to anti-PD-L1 and PD-1 agents such as avelumab and pembrolizumab, respectively. However, real-world data remain sparse. The aim of this study was to assess real-world evidence of the effectiveness of avelumab in a diverse group of patients with MCC in Israel., Methods: The electronic databases of five university hospitals in Israel were searched for all consecutive patients with MCC treated with at least one dose of avelumab in 2018-2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed., Results: The cohort included 62 patients of whom 22% were immune-suppressed. The overall response rate to avelumab was 59%. The median progression-free survival was 8.1 months, and the median overall survival, 23.5 months, with no differences between immune-competent and immune-suppressed patients. Treatment was well tolerated; any-grade toxicity developed in 34% of patients, and grade 3-4 toxicity, in 14%., Conclusions: Avelumab was found to be effective and safe for the treatment of advanced MCC in a diverse group of patients, including some with immune suppression. Further studies are warranted to evaluate the optimal sequence and duration of treatment and to assess the potential role of avelumab for earlier stages of MCC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Standard-of-care treatment for locally advanced esophageal carcinoma (LAEC) includes neoadjuvant chemoradiotherapy followed by esophagectomy. A potentially catastrophic surgical complication is the development of a postoperative anastomotic leak. To date, the association with radiation dose exposure had been inconclusive. We examined the correlation between radiation exposure to the gastric fundus and risk of postoperative leakage using contemporary radiation doses and fractionation., Methods: A total of 69 consecutive patients with LAEC who underwent neoadjuvant chemoradiotherapy followed by esophagectomy in our tertiary center were prospectively followed (median, 27 months). Neoadjuvant regimen included 50.4 Gy in 28 fractions with 5-fluorouracil and cisplatin and 41.4 Gy in 23 fractions with carboplatin and paclitaxel. The gastric fundus was contoured and dosimetric and radiation technique parameters were retrospectively evaluated., Results: Of the total number of patients, 71% and 29% had esophageal and gastroesophageal junction (GEJ) tumors, respectively. Fourteen patients (20.3%) experienced anastomotic leaks within a median of 2 days postoperatively, 78.6% of whom had lower third esophagus or GEJ primaries. Mean and minimum fundus dose did not significantly differ between those with and those without leakage ( p = 0.42, p = 0.51). Mean fundus V25, V30, and V35 doses were numerically but not statistically higher in those with anastomotic leak ( p = 0.58, p = 0.39, and p = 0.30, respectively). No correlation with incidence of leakage was seen between 3D and IMRT treatment modalities., Conclusions: In our comparatively large prospectively collected series of patients treated for LAEC, radiation dose to the gastric fundus during neoadjuvant combination therapy prior to surgery did not correlate with the risk of postoperative anastomotic leak., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kundel, Kurman, Sulimani, Gavrielli, Nachalon, Moore, Kashtan, Fenig, Brenner, Popovtzer and Fredman.)

Purpose: To establish a model to predict treatment outcome of periocular locally advanced basal cell carcinoma (POLA BCC) based on initial response to treatment with vismodegib (Erivedge TM ), a sonic hedgehog inhibitor., Design: Subgroup analysis of data from the STEVIE study database., Methods: Analysis of medical history, treatment protocol, and treatment outcome of POLA BCC tumours in a STEVIE study population of 244 POLA BCC patients treated with ≥1 dose of vismodegib., Results: A predictive model for complete response (CR) was established based on the initial treatment response. A cutoff value of 20% reduction in tumour size at 3 months of treatment identified the patients with a high probability (82.76%) to achieve CR. A second cutoff value of 67.7% reduction in tumour size at 6 months of treatment improved the prediction to a 95.42% probability of a CR outcome., Conclusions: A treatment model was constructed based on the prediction of a CR outcome and the initial response to vismodegib treatment at 3 and 6 months. The study result provide significant new insights can facilitate decision-making on treatment management according to tumour response in patients with POLA BCC., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. It is usually treated surgically, with very high cure rates. However, in 3%-7% of cases, cSCC metastasizes to lymph nodes or distant organs. Many of the affected patients are elderly with comorbidities who are not candidates for standard-of-care curative-intent treatment with surgery and/or radio-/chemotherapy. Immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) pathways, have recently emerged as a potent therapeutic option. The present report presents the Israeli experience with PD-1 inhibitors for the treatment of loco-regionally advanced or metastatic cSCC in a diverse and elderly population, with or without the addition of radiotherapy., Material and Methods: The databases of two university medical centers were retrospectively searched for patients with cSCC treated with the PD-1 inhibitors cemiplimab or pembrolizumab between January 2019 and May 2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed., Results: The cohort included 102 patients of a median age 78.5 years. Evaluable response data were available for 93. The overall response rate was 80.6%: complete response in 42 patients (45.2%) and partial response in 33 (35.5%). Stable disease was recorded in 7 (7.5%) and progressive disease in 11 (11.8%). Median progression-free survival was 29.5 months. Radiotherapy was administered to the target lesion during PD-1 treatment in 22.5% of patients. mPFS was not significantly different in patients who treated with RT than patients how did not (NR vs 18.4 months, HR=0.93, 95%CI: 0.39 - 2.17, p<0.859). Any-grade toxicity was recorded in 57 patients (55%), including grade ‗3 in 25, of whom 5 (5% of cohort) died. Compared to toxicity-free patients, patients with drug toxicity had better progression-free survival (18.4 months vs not reached, HR=0.33, 95% CI: 0.13-0.82, p=0.012) and higher overall response rate (87% vs 71.8%, p=0.06)., Conclusion: This retrospective real-world study showed that PD-1 inhibitors were effective in the treatment of locally advanced or metastatic cSCC and appeared to be amenable for use in elderly or fragile patients with comorbidities. However, the high toxicity warrants consideration against other modalities. Induction or consolidation radiotherapy may improve the results. These findings need to be corroborated in a prospective trial., Competing Interests: GM received a research grant from Sanofi. He is also a consultant advisory board and received honoraria. IF received honoraria from Sanofi and from MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor GB-S declared a shared parent affiliation with the authors SS, ID, and SB at the time of review., (Copyright © 2023 Averbuch, Salman, Shtamper, Doweck, Popovtzer, Markel, Hendler, Finkel, Moore, Fenig, Taha, Mhameed, Kurman and Billan.)

The prognosis of MCC with lymph node involvement was better in patients with an unknown than a known primary. Treatment with a uniform aggressive combined chemoradiation regimen, with or without lymphadenectomy, led to better survival rates than previously reported., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Incidence rates of Merkel cell carcinoma (MCC), an uncommon skin cancer with an aggressive disease course, have increased in recent decades. Limited treatment options are available for patients with metastatic MCC (mMCC). Avelumab, an anti-programmed cell death-ligand 1 monoclonal antibody, became the first approved treatment for mMCC after the results of the phase 2 JAVELIN Merkel 200 study. Prior to its regulatory approval, an expanded access program (EAP) enabled compassionate use of avelumab in patients with mMCC. Here we report findings from patients enrolled in the EAP in Europe and the Middle East. Efficacy and safety data were provided at the discretion of treating physicians. Between March 2, 2016, and December 22, 2018, 403 requests for avelumab were received from 21 countries, and avelumab was supplied to 335 patients. Most patients (96.7%) received avelumab as second-line or later treatment. In 150 patients for whom response data were available, the objective response rate was 48.0%, and in responding patients, median duration of treatment was 7.4 months (range, 1.0-41.7 months). The most common treatment-related adverse events were infusion-related reaction (2.4%) and pyrexia (2.1%), and no new safety signals were observed. Overall, results from European and Middle Eastern patients enrolled in this EAP confirm the efficacy and safety of avelumab treatment observed in previous studies in patients with mMCC., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)