The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy-A Retrospective Multi-Center Cohort Study.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Sulfonamides as anticancer agents: A brief review on sulfonamide derivatives as inhibitors of various proteins overexpressed in cancer.

Sulfonamides have gained prominence as versatile agents in cancer therapy, effectively targeting a spectrum of cancer-associated enzymes. This review provides an extensive exploration of their multifaceted roles in cancer biology. Sulfonamides exhibit adaptability by acting as tyrosine kinase inhibitors, disrupting pivotal signaling pathways in cancer progression. Moreover, they disrupt pH regulation mechanisms in cancer cells as carbonic anhydrase inhibitors, inhibiting growth, and survival. Sulfonamides also serve as aromatase inhibitors, interfering with estrogen synthesis in hormone-driven cancers. Inhibition of matrix metalloproteinases presents an opportunity to impede cancer cell invasion and metastasis. Additionally, their emerging role as histone deacetylase inhibitors offers promising prospects in epigenetic-based cancer therapies. These diverse roles underscore sulfonamides as invaluable tools for innovative anti-cancer treatments, warranting further exploration for enhanced clinical applications and patient outcomes.

Knowledge and competences in hematological malignancies amongst radiation oncology residents in Germany-results from a national survey.

INTRODUCTION: Radiation oncology is a pivotal modality in the treatment of hematologic malignancies. To enable state-of-the-art patient care, structured education during residency is essential. However, given the lack of detailed data, the scope of educational opportunities available to trainees remains elusive. This prompted our group to perform a national survey amongst radiation oncology residents in Germany assessing the status quo of competences in the treatment of lymphoma and leukemia patients. Furthermore, areas of potential improvement were identified to further the goal of competence-based education for residents. METHODS: A survey-based analysis was conducted to assess the knowledge and competence of radiation oncology residents in Germany regarding hematological malignancies. A decisive questionnaire covering demographics, self-assessment of competences, and areas for improvement was developed in adaption of a survey by the Association of Residents in Radiation Oncology and distributed amongst 1439 members of the German Society of Radiation Oncology. Responses were collected anonymously via an online survey tool and analyzed using descriptive statistics and chi-square tests. RESULTS: A total of 59 complete and 22 partial responses were collected, yielding a 5.6% response rate. Participants' competence varied, with notable experience gaps in pediatric cases, proton therapy, and large-field techniques like total-skin irradiation or pediatric total body irradiation. While participants felt confident in treatment planning and patient counseling, they showed deficiencies in the definition of the planning target volume for modern involved site radiotherapy. Resources for education included national and international guidelines, scientific reviews, and textbooks. Board-certified radiation oncologists and physicians from specialized lymphoma centers demonstrated higher overall competence levels. CONCLUSION: This survey highlights the diversity of resident education regarding hematological malignancies in German radiation oncology programs. Knowledge gaps exist in key areas, including pediatric cases and specialized techniques. Competence-based education, interactive teaching formats, and rotations to specialized centers are potential strategies to address these gaps. The study contributes to the understanding of the federal educational landscape, underscoring the need for standardized and comprehensive training to ensure optimal patient care in hematological malignancies within the context of radiation oncology. Further research and collaborations are warranted to enhance training and expertise in this critical domain.

Involved-Site Radiation Therapy Enables Effective Disease Control in Parenchymal Low-Grade Primary Cerebral Lymphoma.

BACKGROUND: Primary lymphoma of the central nervous system (PCNSL) encompasses a variety of lymphoma subtypes, with the majority being diffuse large B-cell lymphomas, which require aggressive systemic treatment. In contrast, low-grade lymphomas are reported infrequently and are mostly limited to dural manifestations. Very rarely, parenchymal low-grade PCNSL is diagnosed, and the cases documented in the literature show a wide variety of treatment approaches. METHODS: We screened all cases of PCNSL treated at our department (a tertiary hematooncology and neurooncology center) in the last 15 years and conducted a comprehensive literature research in the PubMed database. RESULTS: Overall, two cases of low-grade primary parenchymal PCNSL treated with irradiation were identified. The dose prescriptions ranged from 30.6 to 36 Gy for the involved site, with sparing of the hippocampal structures. Both patients had an excellent response to the treatment with a mean follow-up of 20 months. No clinical or radiological signs of treatment toxicity were detected. CONCLUSIONS: Our analysis corroborates the results from the literature and demonstrates that parenchymal low-grade PCNSL shows a good response to localized radiation treatment, enabling a favorable outcome while avoiding long-term treatment toxicity.

Reduction of tumor volume during radiotherapy in patients with small-cell lung cancer and its prognostic significance.

BACKGROUND: Several studies have reported the potential prognostic significance of tumor volume reduction ratio (VRR) induced by radiotherapy (RT) in patients with non-small-cell lung cancer. However, there are no data yet on the prognostic significance of volumetric shrinkage in patients with small-cell lung cancer (SCLC). This study aimed to demonstrate the correlation between tumor volume reduction ratio and treatment outcomes. MATERIALS AND METHODS: The study included 61 patients with SCLC treated with fractionated RT of the primary tumor at our institution between 2013 and 2020. The relationship between volumetric changes in gross tumor volume (GTV) during radiotherapy and outcomes were analyzed and reported. RESULTS: The median radiation dose was 59.4 Gy (median fraction dose was 1.8 Gy). The median GTV before radiotherapy was 74 cm3, with a median GTV reduction of 48%. There was a higher VRR in patients receiving concurrent radiochemotherapy (p = 0.05). No volumetric parameters were identified as relevant predictors of outcome in the entire cohort. In multivariate analysis, only age had an impact on survival, while prophylactic whole-brain radiation influenced the progression-free survival significantly. CONCLUSION: Concurrent chemotherapy was associated with a higher VRR than sequential chemotherapy. No significant impact of VRR on patients' outcome or survival was detected.

Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. MATERIALS AND METHODS: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. RESULTS: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. CONCLUSION: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

The evolving role of reduced-dose total skin electron beam therapy in skin malignancies: the renaissance of a rare indication.

Definitive radiation therapy is an effective local treatment for several cutaneous malignancies. Patients with diffuse or generalized skin manifestations might require total skin electron beam therapy (TSEBT) as an alternative treatment to the chasing technique. In this short communication, we highlight the evolving role of TSEBT and present its role in various forms of skin malignancies.

What Ancient Egyptian Medicine Can Teach Us.

Dr Elsayad describes his impressions regarding the medical and surgical procedures used for patients with cancer and reports on the oncologic cases from ancient Egyptian remains published in the literature.

Impact of dose escalation on colostomy-free survival and treatment outcome in squamous cell anal carcinoma.

PURPOSE: Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer. METHODS: Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). RESULTS: The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3­year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3­year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3­year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3­year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067). CONCLUSION: Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.

Ultrahypofractionated Low-Dose Total Skin Electron Beam in Advanced-Stage Mycosis Fungoides and Sézary Syndrome.

PURPOSE: The aim of this study was to assess the safety and efficacy of an ultrahypofractionated low-dose total skin electron beam therapy (TSEBT) regimen in patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). METHODS AND MATERIALS: In this multicenter observational study from 5 German centers, 18 total patients with MF or SS underwent TSEBT with a total dose of 8 Gy in 2 fractions. The primary endpoint was the overall response rate. RESULTS: Fifteen of 18 patients with stage IIB-IV MF or SS were heavily pretreated with a median of 4 prior systemic therapies. The overall response rate was 88.9% (95% confidence interval [CI], 65.3-98.6), with 3 complete responses (16.9%; 95% CI, 3.6-41.4). At a median follow-up period of 13 months, the median time to next treatment (TTNT) was 12 months (95% CI, 8.2-15.8), and the median progression-free survival was 8 months (95% CI, 2-14). A significant reduction in the modified severity-weighted assessment tool, total Skindex-29 score (Bonferroni-corrected P < .005), and all subdomains (Bonferroni-corrected P < .05) was observed after TSEBT. Half of the irradiated patients (n = 9) developed grade 2 acute and subacute toxicities. One patient had confirmed grade 3 acute toxicity. Chronic grade 1 toxicity has been observed in 33% of patients. Patients with erythroderma/SS or prior radiation therapy appear at higher risk of skin toxicities. CONCLUSIONS: TSEBT with 8 Gy in 2 fractions achieves good disease control and symptom palliation with acceptable toxicity, greater convenience, and fewer hospital visits.

Efficacy of Multimodality Approach in Patients With Recurrent Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is characterized by high relapse rates and low survival in comparison to other malignancies. PATIENTS AND METHODS: Fifty-two patients suffering from recurrent HNSCC were compared, analyzing the impact of different regimes, including surgery, radiotherapy (RT), chemotherapy and immunotherapy on progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and adverse events. RESULTS: The standard RT technique was intensity-modulated radiotherapy (IMRT) in all patients. In the multivariate analysis, higher cumulative RT dose significantly influenced LRC whereas surgery and age significantly impacted PFS and OS. CONCLUSION: IMRT dose-escalation, as well as surgery, appear beneficial in the treatment of recurrent HNSCC. Moreover, nivolumab and platin-based therapy might be superior agents for systemic therapy in comparison to cetuximab.

Low-dose total skin electron beam therapy plus oral bexarotene maintenance therapy for cutaneous T-cell lymphoma.

BACKGROUND: Total skin electron beam therapy (TSEBT) combined with systemic therapy or maintenance treatment is a reasonable approach to enhance the remission rate and duration in mycosis fungoides (MF) and Sézary syndrome (SS). This study assesses the efficacy of oral bexarotene therapy after low-dose TSEBT for patients with MF and SS. METHODS: In this prospective observational study, we recruited MF/SS patients for treatment with low-dose total skin electron beam therapy (TSEBT) with or without bexarotene therapy to describe outcomes and toxicities. RESULTS: Forty-six subjects with MF or SS underwent TSEBT between 2016 and 2021 at our institute. Following TSEBT, 27 patients (59 %) received oral bexarotene treatment. The median follow-up was 13 months. The overall response rate (ORR) for the cohort was 85 %. The response rate was significantly higher with combined modality (CM) than TSEBT alone (96 % vs. 68 %, p = 0.03). Median progression-free survival (PFS) for the CM was 17 months versus five months following TSEBT alone (p = 0.001). One patient (4 %) in the retinoid group discontinued the bexarotene therapy because of adverse events. The administration of bexarotene therapy did not increase radiation-related toxicities. CONCLUSIONS: Response rate and progression-free survival might be improved with TSEBT in combination with oral bexarotene compared to TSEBT alone.

Intensity-modulated Radiotherapy in Patients With Aggressive Extranodal Non-Hodgkin Lymphoma of the Head and Neck.

BACKGROUND/AIM: Image-guided intensity-modulated radiotherapy (IG-IMRT) is increasingly being used to treat patients with head and neck malignancies. This analysis compared conventional radiotherapy (CRT) and IMRT outcomes for head and neck aggressive extranodal non-Hodgkin lymphomas (EN-NHL). PATIENTS AND METHODS: Forty-eight patients who underwent irradiation between 2005 and 2019 were identified. RESULTS: The median follow-up was 42 months. Patients treated with IMRT experienced higher overall responde rate than patients who received 3DCRT (85% vs. 73%, p=0.4). There was non-significant longer survival following IMRT compared with 3DCRT in terms of 5-year OS (p=0.16). Complete responders after primary treatments had a significantly higher 5-year progression-free (p<0.001) and overall survival (p=0.003) in comparison with those without a complete response. Regarding toxicities, IMRT was associated with less acute and chronic adverse events. CONCLUSION: IG-IMRT following systemic therapy seems to be associated with a favorable survival and toxicity profile in patients with EN-NHL.

Impact of Adjuvant Radiotherapy in Patients with Central Neurocytoma: A Multicentric International Analysis.

BACKGROUND: Central neurocytoma (CN) is a rare tumor accounting for <0.5% of all intracranial tumors. Surgery ± radiotherapy is the mainstay treatment. This international multicentric study aims to evaluate the outcomes of CNs patients after multimodal therapies and identify predictive factors. PATIENTS AND METHODS: We retrospectively identified 33 patients with CN treated between 2005 and 2019. Treatment characteristics and outcomes were assessed. RESULTS: All patients with CN underwent surgical resection. Radiotherapy was delivered in 19 patients. The median radiation dose was 54 Gy (range, 50-60 Gy). The median follow-up time was 56 months. The 5-year OS and 5-year PFS were 90% and 76%, respectively. Patients who received radiotherapy had a significantly longer PFS than patients without RT (p = 0.004) and a trend towards longer OS. In addition, complete response after treatments was associated with longer PFS (p = 0.07). CONCLUSIONS: Using RT seems to be associated with longer survival rates with an acceptable toxicity profile.