Nationwide Analysis of Locoregional Management for Ductal Carcinoma In Situ in Males: An NCDB Analysis of the Surgical Approach to DCIS in Males.

BACKGROUND: Limited data exist regarding the optimal locoregional approach for males with ductal carcinoma in situ (DCIS). This study examined trends in management and survival for males with DCIS. METHODS: The National Cancer Database (NCDB) was queried for males with a diagnosis of DCIS from 2006 to 2017. Patients were categorized by locoregional management. Continuous variables were evaluated by Kruskal-Wallis and categorical variables by chi-square or Fisher's exact test. Univariable and multivariable logistic regressions were performed to evaluate for predictors of patients receiving partial mastectomy (PM) with radiation. Survival was analyzed by Kaplan-Meier. RESULTS: Between 2006 and 2017, 711 males with DCIS were identified. Most received mastectomy alone (57.1%). No change was observed in management approach from 2006 to 2017. Patients who underwent mastectomy alone were mostly hormone-positive (95.9% were estrogen-positive, 90.9% were progesterone-positive), although this cohort was least likely to receive hormone therapy (17.2%). Among those who underwent PM with radiation, only 61% of those who were hormone-positive received hormone therapy. Univariable analysis demonstrated that those of black race had lower odds of receiving PM with radiation (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.36-0.84), which persisted in the multivariable analysis with control for age and tumor size (OR, 0.32; 95% CI, 0.15-0.67). Overall survival did not differ significantly between the four treatment methods (p = 0.08). CONCLUSIONS: The management approach to male DCIS did not change from 2006 to 2017. Survival did not differ between treatment methods. Demographic and clinicopathologic features, including race, may influence locoregional treatments received, and further studies are needed to further understand this.

Feasibility Trial of Intensity Modulated Proton Therapy to Reduce Toxicity in Anal Cancer Patients.

PURPOSE: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT). METHODS: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529. RESULTS: Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment. CONCLUSIONS: Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation.

Application of the patient-reported outcomes continual reassessment method to a phase I study of radiotherapy in endometrial cancer.

This article considers the concept of designing Phase I clinical trials using both clinician- and patient-reported outcomes to adaptively allocate study participants to tolerable doses and determine the maximum tolerated dose (MTD) at the study conclusion. We describe an application of a Bayesian form of the patient-reported outcomes continual reassessment method (PRO-CRMB) in an ongoing Phase I study of adjuvant hypofractionated whole pelvis radiation therapy (WPRT) in endometrial cancer (NCT04458402). The study's primary objective is to determine the MTD per fraction of WPRT, defined by acceptable clinician- and patient-reported DLT rates. We conduct simulation studies of the operating characteristics of the design and compared them to a rule-based approach. We illustrate that the PRO-CRMB makes appropriate dose assignments during the study to give investigators and reviewers an idea of how the method behaves. In simulation studies, the PRO-CRMB demonstrates superior performance to a 5 + 2 stepwise design in terms of recommending target treatment courses and allocating patients to these courses. The design is accompanied by an easy-to-use R shiny web application to simulate operating characteristics at the design stage and sequentially update dose assignments throughout the trial's conduct.

Hematologic Toxicity Comparison of Intensity Modulated Proton Therapy and Intensity Modulated Radiation Therapy in Anal Cancer Patients.

PURPOSE: We hypothesize that hematologic toxicity will be lower in anal cancer patients treated definitively with intensity modulated proton therapy (IMPT) compared with patients treated with intensity modulated radiation therapy (IMRT). METHODS: Patients enrolled on a prospective feasibility trial assessing the use of IMPT for anal cancer were compared with contemporaneous patients treated with IMRT. Blood counts were collected during chemoradiation. Hematologic events were graded according to CTCAE version 5.0. Pelvic bone marrow (PBM) and positron emission tomography-defined active bone marrow (ABM) were defined and contoured for each patient. Toxicity rates, PBM and ABM dose metrics were compared between groups. RESULTS: Forty-one patients treated with definitive chemoradiation for anal cancer between 2015 and 2021 were included in this analysis. Of the evaluable patients, 14 patients were treated with IMPT and 27 were treated with IMRT. All PBM dose metrics were lower in patients receiving IMPT. Patients treated with IMPT versus IMRT also had a significantly lower ABM mean dose (1996 vs. 3073 Gy, P<0.01). However, there was no statistically significant difference in hematologic toxicity between the groups. Seventy percent of patients treated with IMRT had at least 1 grade ≥3 hematologic event compared with 86% in the IMPT group (P=0.48). CONCLUSION: Proton treatment reduced bone marrow doses but was not associated with lower hematologic toxicity when compared with IMRT.

Trends and Outcomes Associated With Axillary Management of Males With Clinical N0 Breast Cancer-An NCDB Analysis.

BACKGROUND: Sentinel Lymph Node Biopsy (SLNB) is standard of care for women with clinically N0 breast cancer. However, there are no randomized controlled studies in men determining optimal surgical axillary management. METHODS: Using the National Cancer Database, males diagnosed from 2006-2016 with clinical T1-4 N0 tumors treated with primary surgery were identified and categorized by axillary management. Clinicopathologic variables were compared between two timeframes, 2006-2011 and 2012-2016. Survival analysis was performed. RESULTS: We identified 2,646 males meeting criteria. Use of SLNB increased (65.9%-72.8%, P < 0.01). For those who underwent ALND, administration of radiation (31.1% versus 48.8%, P < 0.01) and endocrine therapy (70.2% versus 80.7%, P < 0.01) increased. There was no difference in survival between timeframes (P = 0.42). For those who underwent SLNB, tumor grade (P = 0.02) and pathologic T stage (P < 0.01) were higher and more patients underwent mastectomy (74.9% versus 79.4%, P = 0.02). Administration of chemotherapy decreased (35.1% versus 27.2%, P < 0.01) and endocrine therapy increased (72.1% versus 81.3%, P < 0.01). Survival of those who underwent sentinel lymph node biopsy (SLNB) diagnosed 2012-2016 was worse than those diagnosed 2006-2011 (P = 0.01). CONCLUSIONS: Use of SLNB alone has increased while ALND has declined in males with clinically N0 breast cancer. However, patients who underwent SLNB alone in the later time period had worse clinical characteristics and experienced differences in adjuvant therapy. This suggests increased acceptance of the use of SLNB for axillary management. Further analysis is warranted to evaluate methods of axillary staging and the impact on outcomes in males with breast cancer.

The value of hybrid interstitial tandem and ring applicators for organ at risk dose reduction in small volume cervical cancer.

PURPOSE: Magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the standard of care for cervical cancer. Hybrid intracavitary/interstitial applicators for bulky tumor (high-risk clinical target volume [HR-CTV] > 30 cc) dose escalation is recommended in the EMBRACE II trial. The value of hybrid applicators for smaller HR-CTV (< 30 cc) in organ at risk (OAR) sparing is less certain. MATERIAL AND METHODS: Twenty-seven patients with FIGO stage I-IVA cervical cancer treated with definitive chemoradiation and MRI-based brachytherapy using conventional tandem and ring (TR) applicators were re-planned using virtual needles. They were then summed with the external beam dose to evaluate target coverage and OAR dose using EQD2 summation. Target and OAR dose with/without hybrid applicator use were compared. RESULTS: Eighty-one percent had HR-CTV volumes < 30 cc, for which, hybrid TR applicators had significantly lower mean D2cc to all OARs without differences in target coverage. For HR-CTV < 30 cc, the bladder and rectal OAR goals per EMBRACE II were exceeded in significantly fewer patients with the hybrid TR applicators. No significant difference was found in the sigmoid D2cc dose goal. CONCLUSIONS: In small volume tumors (< 30 cc), hybrid applicators may offer improved OAR sparing compared with conventional tandem and ring applicators, and may increase the proportion of patients meeting EMBRACE II OAR goals.

Comparison of spinal and general anesthesia approaches for MRI-guided brachytherapy for cervical cancer.

PURPOSE: To evaluate the impact of general versus spinal anesthesia on postprocedure narcotic use and of extradepartmental planning MRI on treatment time in high-dose-rate brachytherapy for cervical cancer. METHODS AND MATERIALS: Twenty-five patients (10 general anesthesia and 15 spinal anesthesia) who collectively received 96 brachytherapy fractions (39 general and 57 spinal) for cervical cancer between February 2015 and April 2017 were retrospectively reviewed. Over this time, institutional practice shifted from operating room-based general anesthesia to intradepartmental spinal anesthesia for tandem and ring placement. In some cases, extradepartmental planning MRI was performed. Administrations of narcotics after tandem and ring placement were recorded, and dosages were converted to intravenous (IV) morphine equivalents. Total treatment times for fractions using spinal anesthesia were documented. RESULTS: The general anesthesia group included a significantly higher proportion of fractions using postprocedure narcotics (100.0% vs. 31.6%, p < 0.0001). The general and spinal anesthesia groups required an average of 16.9 mg (range: 2.0-59.2) and 1.4 mg (range: 0.0-17.5) IV morphine equivalents per fraction, respectively (p < 0.0001). When using spinal anesthesia, the average total treatment time with MRI was 311.0 min (range: 218-379) versus 306.6 min (range: 177-429) without MRI (p = 0.810). CONCLUSION: Intradepartmental spinal anesthesia results in significant decreases in postprocedure narcotic usage compared with operating room-based general anesthesia. When using spinal anesthesia, addition of extradepartmental MRI does not increase treatment time. This workflow avoids transporting patients under general anesthesia, minimizes the need for MRI-compatible monitoring, allows treatment of multiple patients per day, and provides adequate analgesia.

Dosimetric Comparison of Intensity-Modulated Proton Therapy and Volumetric-Modulated Arc Therapy in Anal Cancer Patients and the Ability to Spare Bone Marrow.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has been used to spare organs at risk (OARs) in the definitive treatment of anal cancer. However, treatment continues to result in significant hematologic toxicity. In a cooperative trial assessing IMRT (RTOG 0529), the rate of grade 2+ and grade 3+ hematologic toxicity was 73% and 58%, respectively. Intensity-modulated proton therapy (IMPT) has the potential to decrease the integral bone marrow dose and dose to other OARs compared with photon therapy. PATIENTS AND METHODS: Computed tomography datasets of 9 patients with anal cancer previously treated with IMRT, volumetric arc therapy (VMAT), or tomotherapy at our institution were used for comparison. Both VMAT and IMPT plans were created for each patient. The IMPT plans were created using a multi-field optimized, split-target technique. The dose to OARs, including bone marrow, bladder, small bowel, large bowel, femoral heads, and genitalia, were compared using a paired t test. RESULTS: The mean bone marrow dose was 17.42 Gy with IMPT plans and 30.76 Gy with VMAT plans (P < .0001). The absolute volume of bone marrow spared 10 and 20 Gy was significantly less with the proton plans. IMPT also showed significant sparing of other OARs, including the small and large bowel, femoral heads, and genitalia. The mean planning target volume receiving at least 95% of the prescribed dose (V95) was similar with IMPT and VMAT plans, 99% and 98%, respectively. CONCLUSION: IMPT can decrease the mean bone marrow dose compared with VMAT plans by minimizing the low dose spill associated with standard photon treatment. Prospective studies assessing proton therapy for anal cancer are ongoing to evaluate the potential for improvement in hematologic toxicity and the acute tolerance of therapy.

A rare case of central nervous system amyloidoma treated with fractionated radiotherapy.

A 54-year-old female presented with multiple episodes of emesis, intractable headaches, worsening balance, and slowly progressive right facial weakness. Imaging demonstrated a 3-cm mass in the left internal capsule and corona radiata region with associated edema, mass effect, and midline shift concerning for high-grade glioma, lymphoma, or brain metastasis. Stereotactic biopsy of the mass was consistent with amyloid deposition. Systemic workup for amyloidosis was negative, and the mass was thought to represent a focal tumor-like deposit of amyloid, also referred to as "amyloidoma." In the absence of systemic disease, therapy, which can include surgery or radiotherapy, can be directed at the local process. The location of the patient's lesion was not amenable to resection; therefore, she was treated with fractionated radiotherapy of 30.6 Gy at 1.8 Gy per fraction. Serial brain MRI demonstrated stability 18 months out from therapy. To the authors' knowledge, this is the first documented case of focal fractionated radiotherapy for CNS amyloidoma. The authors concluded that radiotherapy can prevent further progression of amyloidomas in anatomical locations that prohibit resection.