Combining Obinutuzumab With Radiation for Refractory DLBCL: Retrospective Safety and Efficacy Analysis.

Purpose: Approximately 30% of patients with diffuse large B cell lymphoma (DLBCL) will develop relapsed or treatment-refractory disease after primary chemotherapy. Patients unable to undergo aggressive chemotherapy and stem cell transplant or chimeric antigen receptor T-cell (CAR T-cell) therapy have limited treatment options. Here, we investigated the safety and efficacy of combining obinutuzumab with cytoreductive radiation to all areas of disease in patients with relapsed DLBCL. Methods and Materials: A retrospective review of patients with treatment refractory DLBCL was performed. All patients were treated with external beam radiation to all sites of refractory disease with concurrent and adjuvant obinutuzumab. Toxicities were evaluated based on Common Terminology Criteria for Adverse Events v5.0 criteria. Kaplan-Meier analysis was used to calculate progression-free survival and overall survival. Results: Between 2016 and 2022, 7 patients with refractory DLBCL were treated with concurrent radiation and obinutuzumab. No grade 3 or greater treatment-related toxicity was observed. Four of the 7 patients had a complete response at the radiated site on first postradiation imaging. The median progression-free survival and overall survival were 30 months. Conclusions: In this small cohort of treatment-refractory patients with DLBCL, the combination of radiation and obinutuzumab was well tolerated without excessive treatment-related toxicity. The combination resulted in durable disease control with a prolonged overall survival without additional treatment in a subset of patients.

Implementation of an intervention aimed at deprescribing benzodiazepines in a large US healthcare system using patient education materials: a pre/post-observational study with a control group.

OBJECTIVES: Long-term benzodiazepine use is common despite known risks. In the original Eliminating Medications Through Patient Ownership of End Results (EMPOWER) Study set in Canada, patient education led to increased rates of benzodiazepine cessation. We aimed to determine the effectiveness of implementing an adapted EMPOWER quality improvement (QI) initiative in a US-based healthcare system. DESIGN: We used a pre-post design with a non-randomised control group. SETTING: A network of primary care clinics. PARTICIPANTS: Patients with ≥60 days' supply of benzodiazepines in 6 months and ≥1 risk factor (≥65 years of age, a concurrent high-risk medication prescribed or a diazepam equivalent daily dose ≥10) were eligible. INTERVENTION: In March 2022, we engaged 22 primary care physicians (PCPs), and 308 of their patients were mailed an educational brochure, physician letter and flyer detailing benzodiazepine risks; the control group included 4 PCPs and 291 of their patients. PRIMARY AND SECONDARY MEASURES: The primary measure was benzodiazepine cessation by 9 months. We used logistic regression and a generalised estimating equations approach to control for clustering by PCP, adjusting for demographics, frailty, number of risk factors, and diagnoses of arthritis, depression, diabetes, falls, and pain. RESULTS: Patients in the intervention and control groups were comparable across most covariates; however, a greater proportion of intervention patients had pain-related diagnoses and depression. By 9 months, 26% of intervention patients (81 of 308) had discontinued benzodiazepines, compared with 17% (49 of 291) of control patients. Intervention patients had 1.73 greater odds of benzodiazepine discontinuation compared with controls (95% CI: 1.09, 2.75, p=0.02). The unadjusted number needed to treat was 10.5 (95% CI: 6.30, 34.92) and the absolute risk reduction was 0.095 (95% CI: 0.03 to 0.16). CONCLUSIONS: Results from this non-randomised QI initiative indicate that patient education programmes using the EMPOWER brochures have the potential to promote cessation of benzodiazepines in primary care.

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial.

PURPOSE: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Effect of COVID-19 on Gynecologic Oncology Care: A Survey of Practicing Gynecologic Radiation Oncologists in the United States.

Purpose: The COVID-19 pandemic has placed demands and limitations on the delivery of health care. We sought to assess the effect of COVID-19 on the delivery of gynecologic oncologic care from the perspective of practicing radiation oncologists in the United States. Methods and Materials: An anonymous online survey was created and distributed to preidentified radiation oncologists in the United States with clinical expertise in the management of gynecologic patients. The survey consisted of demographic questions followed by directed questions to assess specific patterns of care related to the COVID-19 pandemic. Results: A total of 47 of 96 invited radiation oncologists responded to the survey for a response rate of 49%. Fifty-six percent of respondents reported an increase in locally advanced cervical cancer with no similar increase for endometrial, vulvar, or vaginal patients. Most respondents (66%) reported a pause in surgical management, with a duration of 1 to 3 months being most common (61%). There was a reported increased use of shorter brachytherapy regimens during the pandemic. Most providers (61%) reported caring for at least 1 patient with a positive COVID-19 test. A pause or delay in treatment due to COVID-19 positivity was reported by 45% of respondents, with 55% reporting that patients chose to delay their own care because of COVID-19-related concerns. Total treatment times >8 weeks for patients with cervical cancer were observed by 33% of respondents, but occurred in >25% of patients. Conclusions: Data from this prospectively collected anonymous survey of practice patterns among radiation oncologists reveal that the COVID-19 pandemic resulted in delays initiating care, truncated brachytherapy treatment courses, and a reported increase in locally advanced cervical cancer cases at presentation. These data can be used as a means of self-assessment to ensure appropriate decision making for gynecologic patients during the endemic phase of COVID-19.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.

Design, implementation, and evaluation of a pharmacist-led outpatient benzodiazepine-tapering clinic.

BACKGROUND: Benzodiazepines are commonly used among older adults, despite well-known risks. Clinical pharmacists can lead tapering efforts, leveraging their clinical expertise and relieving time-pressured primary care providers. OBJECTIVES: The objective of this study is to describe the design, implementation, and evaluation of an outpatient pharmacist-led benzodiazepine-tapering clinic. PRACTICE DESCRIPTION: The clinic is based within a community medical group associated with a large academic health system in Los Angeles, California. PRACTICE INNOVATION: The clinic is staffed by clinical pharmacists and supervised by a psychiatrist. The initial visit consists of patient education, design of patient-driven tapering schedule, and medical history review. Follow-up phone/video visits are used to monitor withdrawal symptoms and provide support. EVALUATION METHODS: We used chart review to assess tapering status among those enrolled in the tapering clinic versus those who did not enroll. We compared outcomes across the 2 groups using bivariate statistics. RESULTS: From March 2017 to May 2019, 176 patients were referred to the clinic; 17 were deemed ineligible. Of the 159 patients contacted, 62 patients enrolled in the clinic; 97 patients did not enroll. Among patients in the clinic, 13 (27%) of patients were tapered down, 29 (60%) completely tapered off, 6 (13%) were unable to taper, and 14 (23%) were in the process of tapering. In contrast, among patients who did not enroll, 3 (4%) of patients were tapered down, 15 (20%) completely tapered off, 57 (76%) were unable to taper, and 22 (22%) were in the process of tapering. Ninety percent of patients had at least some benzodiazepine tapering when enrolled in the clinic compared to 41% among not enrolled in the clinic (P<0.001). CONCLUSION: A pharmacist-led benzodiazepine-tapering clinic can be an effective way to engage patients motivated to taper down. Lessons learned include the importance of ensuring referring providers adequately counsel patients prior to referral.

Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline.

PURPOSE: With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, and the effect of surgical staging techniques and molecular tumor profiling. METHODS: The American Society for Radiation Oncology convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the (1) indications for adjuvant RT, (2) RT techniques, target volumes, dose fractionation, and treatment planning aims, (3) indications for systemic therapy, (4) sequencing of systemic therapy with RT, (5) effect of lymph node assessment on utilization of adjuvant therapy, and (6) effect of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS: The task force recommends RT (either vaginal brachytherapy or external beam RT) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When external beam RT is delivered, intensity modulated RT with daily image guided RT is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II with high-risk histologies and those with FIGO stage III to IVA with any histology. When sequencing chemotherapy and RT, there is no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging. Data on sentinel lymph node pathologic ultrastaging status supports that patients with isolated tumor cells be treated as node negative and adjuvant therapy based on uterine risk factors and patients with micrometastases be treated as node positive. The available data on molecular characterization of endometrial cancer are compelling and should be increasingly considered when making recommendations for adjuvant therapy. CONCLUSIONS: These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.

Targeting the GTV in medically inoperable endometrial cancer using brachytherapy.

PURPOSE: We aimed to determine the relationship between gross tumor volume (GTV) dose and tumor control in women with medically inoperable endometrial cancer, and to demonstrate the feasibility of targeting a GTV-focused volume using imaged-guided brachytherapy. METHODS AND MATERIALS: An endometrial cancer database was used to identify patients. Treatment plans were reviewed to determine doses to GTV, clinical target volume (CTV), and OARs. Uterine recurrence-free survival was evaluated as a function of CTV and GTV doses. Brachytherapy was replanned with a goal of GTV D98 EQD2 ≥ 80 Gy, without regard for coverage of the uninvolved uterus and while respecting OAR dose constraints. RESULTS: Fifty-four patients were identified. In the delivered plans, GTV D90 EQD2 ≥ 80 Gy was achieved in 36 (81.8%) patients. Uterine recurrence-free survival was 100% in patients with GTV D90 EQD2 ≥ 80 Gy and 66.7% in patients with EQD2 < 80 Gy (p = 0.001). On GTV-only replans, GTV D98 EQD2 ≥ 80 Gy was achieved in 39 (88.6%) patients. Mean D2cc was lower for bladder (47.1 Gy vs. 73.0 Gy, p < 0.001), and sigmoid (47.0 Gy vs. 58.0 Gy, p = 0.007) on GTV-only replans compared to delivered plans. Bladder D2cc was ≥ 80 Gy in 11 (25.0%) delivered plans and four (9.1%) GTV-only replans (p = 0.043). Sigmoid D2cc was ≥ 65 Gy in 20 (45.4%) delivered plans and 10 (22.7%) GTV-only replans (p = 0.021). CONCLUSIONS: OAR dose constraints should be prioritized over CTV coverage if GTV coverage is sufficient. Prospective evaluation of image-guided brachytherapy to a reduced, GTV-focused volume is warranted.

NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Four Ways to Decrease Late Toxicity From Pelvic Radiation Therapy in Children and Young Adults.

The use of curative-intent multimodality therapy with chemotherapy, surgery, and radiation results in late toxicities in almost two-thirds of patients with pediatric cancer. When pelvic radiation is used for pediatric malignancies such as rhabdomyosarcoma, lymphoma, neuroblastoma, Ewing sarcoma, and Wilms tumor, the associated late toxicities can affect many normal tissues and may include growth asymmetries, cystitis, infertility, and sexual dysfunction. We describe 4 recommendations of how to prevent or minimize late toxicities from pelvic radiation and review the literature of these pediatric late toxicities.

Rare tumors: Retinoblastoma, nasopharyngeal cancer, and adrenocorticoid tumors.

The role of surgery, chemotherapy, and radiation therapy for retinoblastoma has evolved considerably over the years with the efficacy of intraarterial chemotherapy and the high incidence of secondary malignant neoplasms following radiation therapy. The use of spot scanning intensity-modulated proton therapy may reduce the risk of secondary malignancies. For pediatric nasopharyngeal carcinoma, the current standard of care is induction chemotherapy followed by chemoradiation therapy. For adrenocortical carcinoma, the mainstay of treatment is surgery and chemotherapy. The role of radiation therapy remains to be defined.

Comparison of catheter reconstruction techniques for the lunar ovoid channels of the VeneziaTM applicator.

PURPOSE: The aim of this study was to compare catheter reconstruction methods for lunar ovoid channels of the VeneziaTM advanced gynecological applicator (Elekta, Sweden). MATERIAL AND METHODS: Three available lunar ovoid sizes (22, 26, and 30 mm effective diameter) were evaluated. Computed tomography (CT) scans were performed with a dummy wire inserted and with the Flexitron® source position simulator (SPS) at step sizes of 5 mm from the most distal dwell position. Treatment plans were generated in Oncentra® (version 4.5.3) with different catheter reconstruction techniques: centerline reconstruction, tracing a CT dummy wire, using a source path model provided by Elekta, and using the SPS at each planning dwell position. Source position agreement was assessed in registered CT images, and dose differences were calculated with the SPS-based treatment plan as a reference. Finally, dose-volume histogram (DVH) parameters were evaluated for clinical plans with the VeneziaTM applicator. RESULTS: For the most distal dwell position, the manufacturer's model had the closest agreement with the SPS at 0.6 ±0.3 mm across applicator sizes. Relative to the SPS, maximal dose differences outside of the applicator were between 16-39% for a 0.1 cm3 volume and 3.6-9.1% for a 2.0 cm3 volume. For two clinical plans, volume-based DVH parameters agreed ≤ 3.9%, while deviations ≤ 5.3% were seen for point metrics. CONCLUSIONS: Relative to the SPS-based plan, large local dose discrepancies were reduced, but not eliminated, using the manufacturer's source path model. The choice of reconstruction technique was found to have relatively limited impact on DVH parameters for regions outside of the vaginal mucosa.