Emma C. Fields

Management of Male Breast Cancer in the United States: A Surveillance, Epidemiology and End Results Analysis

PURPOSE To analyze the stage-specific management of male breast cancer (MBC) with surgery and radiation therapy (RT) and relate them to outcomes and to female breast cancer (FBC). METHODS AND MATERIALS The Surveillance, Epidemiology, and End Results database was queried for all primary invasive MBC and FBC diagnosed from 1973 to 2008. Analyzable data included age, race, registry, grade, stage, estrogen and progesterone receptor status, type of surgery, and use of RT. Stage was defined as localized (LocD): confined to the breast; regional (RegD): involving skin, chest wall, and/or regional lymph nodes; and distant: M1. The primary endpoint was cause-specific survival (CSS). RESULTS A total of 4276 cases of MBC and 718,587 cases of FBC were identified. Male breast cancer constituted 0.6% of all breast cancer. Comparing MBC with FBC, mastectomy (M) was used in 87.4% versus 38.3%, and breast-conserving surgery in 12.6% versus 52.6% (P<10(-4)). For males with LocD, CSS was not significantly different for the 4.6% treated with lumpectomy/RT versus the 70% treated with M alone (hazard ratio [HR] 1.33; 95% confidence interval [CI] 0.49-3.61; P=.57). Postmastectomy RT was delivered in 33% of males with RegD and was not associated with an improvement in CSS (HR 1.11; 95% CI 0.88-1.41; P=.37). There was a significant increase in the use of postmastectomy RT in MBC over time: 24.3%, 27.2%, and 36.8% for 1973-1987, 1988-1997, and 1998-2008, respectively (P<.0001). Cause-specific survival for MBC has improved: the largest significant change was identified for men diagnosed in 1998-2008 compared with 1973-1987 (HR 0.73; 95% CI 0.60-0.88; P=.0004). CONCLUSIONS Surgical management of MBC is dramatically different than for FBC. The majority of males with LocD receive M despite equivalent CSS with lumpectomy/RT. Postmastectomy RT is greatly underutilized in MBC with RegD, although a CSS benefit was not demonstrated. Outcomes for MBC are improving, attributable to improved therapy and its use in this unscreened population.

Phase I Dose Escalation Trial of Vandetanib With Fractionated Radiosurgery in Patients With Recurrent Malignant Gliomas

PURPOSE To determine the maximum tolerated dose (MTD) of vandetanib with fractionated stereotactic radiosurgery (SRS) in patients with recurrent malignant gliomas. METHODS AND MATERIALS Patients with a recurrent malignant glioma and T1-enhancing recurrent tumor ≤ 6 cm were eligible. Vandetanib was given orally, once per day, 7 days a week, starting at least 7 days before SRS and continued until a dose-limiting toxicity (DLT) or disease progression. The planned vandetanib daily dose was 100 mg, 200 mg, and 300 mg for the cohorts 1, 2, and 3, respectively, and was escalated using a standard 3+3 design. A total SRS dose of 36 Gy, 12 Gy per fraction, was delivered over 3 consecutive days. The MTD was defined as the dose of vandetanib at which less than 33% of patients developed DLTs, defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3 as any Grade 3 or greater nonhematologic toxicity and Grade 4 or greater hematologic toxicity. RESULTS Ten patients were treated, 6 on cohort 1 and 4 on cohort 2. Treatment characteristics were: 7 men, 3 women; median age, 40 years (range, 22-72); 7 GBM, 3 anaplastic astrocytoma (AA); median initial radiation (RT) dose, 60 Gy (range, 59.4-70); median interval since initial RT, 14.5 months (range, 7-123); All patients received SRS per protocol. The median follow-up time was 4 months (range, 1-10 months). Median time on vandetanib was 3 months (range 1-11). One of 6 patients in the first cohort developed a DLT of Grade 3 hemothorax while on anticoagulation. The MTD was reached when 2 of the 4 patients enrolled in the second cohort developed DLTs. Six patients had radiographic response, 2 with stable disease. CONCLUSION The MTD of vandetanib, with SRS in recurrent malignant glioma, is 100 mg daily. Further evaluation of safety and efficacy is warranted.

A practical review of magnetic resonance imaging for the evaluation and management of cervical cancer

Cervical cancer is a leading cause of mortality in women worldwide. Staging and management of cervical cancer has for many years been based on clinical exam and basic imaging such as intravenous pyelogram and x-ray. Unfortunately, despite advances in radiotherapy and the inclusion of chemotherapy in the standard plan for locally advanced disease, local control has been unsatisfactory. This situation has changed only recently with the increasing implementation of magnetic resonance image (MRI)-guided brachytherapy. The purpose of this article is therefore to provide an overview of the benefits of MRI in the evaluation and management of cervical cancer for both external beam radiotherapy and brachytherapy and to provide a practical approach if access to MRI is limited.

A detailed evaluation of TomoDirect 3DCRT planning for whole-breast radiation therapy

The goal of this work was to develop planning strategies for whole-breast radiotherapy (WBRT) using TomoDirect three-dimensional conformal radiation therapy (TD-3DCRT) and to compare TD-3DCRT with conventional 3DCRT and TD intensity-modulated radiation therapy (TD-IMRT) to evaluate differences in WBRT plan quality. Computed tomography (CT) images of 10 women were used to generate 150 WBRT plans, varying in target structures, field width (FW), pitch, and number of beams. Effects on target and external maximum doses (EMD), organ-at-risk (OAR) doses, and treatment time were assessed for each parameter to establish an optimal planning technique. Using this technique, TD-3DCRT plans were generated and compared with TD-IMRT and standard 3DCRT plans. FW 5.0cm with pitch = 0.250cm significantly decreased EMD without increasing lung V20Gy. Increasing number of beams from 2 to 6 and using an additional breast planning structure decreased EMD though increased lung V20Gy. Changes in pitch had minimal effect on plan metrics. TD-3DCRT plans were subsequently generated using FW 5.0cm, pitch = 0.250cm, and 2 beams, with additional beams or planning structures added to decrease EMD when necessary. TD-3DCRT and TD-IMRT significantly decreased target maximum dose compared to standard 3DCRT. FW 5.0cm with 2 to 6 beams or novel planning structures or both allow for TD-3DCRT WBRT plans with excellent target coverage and OAR doses. TD-3DCRT plans are comparable to plans generated using TD-IMRT and provide an alternative to conventional 3DCRT for WBRT.

Radiation Treatment in Women with Ovarian Cancer: Past, Present, and Future

Ovarian cancer is the most lethal of the gynecologic cancers, with 5-year survival rates less than 50%. Most women present with advanced stage disease as the pattern of spread is typically with dissemination of malignancy throughout the peritoneal cavity prior to development of any symptoms. Prior to the advent of platinum-based chemotherapy, radiotherapy was used as adjuvant therapy to sterilize micrometastatic disease. The evolution of radiotherapy is detailed in this review, which establishes radiotherapy as an effective therapy for women with micrometastatic disease in the peritoneal cavity after surgery, ovarian clear cell carcinoma, focal metastatic disease, and for palliation of advanced disease. However, with older techniques, the toxicity of whole abdominal radiotherapy and the advancement of systemic therapies have limited the use of radiotherapy in this disease. With newer radiotherapy techniques, including intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and low-dose hyperfractionation in combination with targeted agents, radiotherapy could be reconsidered as part of the standard management for this deadly disease.

Changing paradigm in pancreatic cancer: from adjuvant to neoadjuvant chemoradiation

BACKGROUND Historically, management of pancreatic cancer has been determined based on whether the tumor was amenable to resection and all patients deemed resectable received curative intent surgery followed by adjuvant therapy with chemotherapy (CT) ± RT. However, patients who undergo resection with microscopic (R1) positive margins have inferior rates of survival. The purpose of this study is to identify patients who have undergone pancreatectomy for pancreatic cancer, determine the surgical margins, types of adjuvant therapies given and patterns of failure. Our hypothesis was that in patients who have surgery without pre-operative therapy, there is a high rate of R1 resections and subsequent local recurrence, despite adjuvant therapy. METHODS Seventy-one patients with curative resections for pancreatic cancer between 2003 and 2015 were reviewed. Tumor stage, margin status, distance to closest margin, receipt of adjuvant therapy and length of survival were collected. Patients were divided into two groups based on whether they received adjuvant CT + RT (n=37) or CT alone (n=37). Patients were further divided based on whether resection was R1 (n=29) or R0 (n=42). Wilcoxon survival tests and Cox proportional hazards regression models were performed to determine the effects of CT + RT vs. CT alone, stratified by surgical margin status. RESULTS Of the 29 patients (39%) who had R1, 15 received CT + RT and 14 received only CT. Patients who received CT + RT experienced a significantly longer period of PFS (13 vs. 7.5 mos, P=0.03) than patients who received CT alone. However, there was no significant difference found in time to death post cancer resection between CT + RT vs. CT alone (P=0.73). Of the 42 patients with R0, 21 received CT + RT and 21 received CT. There was a trend towards increase in PFS in patients treated with CT + RT (25 vs. 17 months, P=0.05), but there was no significant increase in time to death compared to patients treated with CT alone (P=0.53. Of the 36 patients with CT + RT, 21 had R0 and 15 had R1. Patients with R0 were more likely to have longer PFS (25 vs. 13 months, P=0.06), but there was no significant difference in time to death compared to patients with CT alone (P=0.68). CONCLUSIONS After curative resection, the addition of RT to CT improves PFS in both R0 and R1 settings. However, patients with R1 have significantly worse PFS and OS compared to patients with R0 and even aggressive adjuvant therapy does not make up for the difference. The paradigm has shifted and now for patients with resectable pancreatic cancers we recommend neoadjuvant CT + RT to improve RT targeting and treatment response assessment and most importantly, improve chances of obtaining R0.

Racial differences in responses to the NCCN Distress Thermometer and Problem List: Evidence from a radiation oncology clinic

Initiation of radiation therapy for cancer patients can be a distressing experience, posing a unique set of challenges, including daily treatments requiring reliable transportation, and patients may experience related medical costs, pain, and other side effects. Distress has been shown to be common in the radiation oncology setting, where up to 37% of patients reported distress at some point during treatment. The National Comprehensive Cancer Network (NCCN) recommends screening all cancer patients for distress using an ordinal Distress Thermometer (DT) (scoring 0‐10) and Problem List (PL) questionnaire to identify patients who may benefit from intervention of social support or mental health services. This survey method has been validated against multiple mental health batteries. The extensive PL questionnaire accompanying the DT, covering practical, family, emotional, spiritual, and physical concerns, allows a unique opportunity to analyze the components that contribute to patient distress. The racial disparities in multiple outcomes, including survival, for cancer patients are widely established. Specifically, African American cancer patients, regardless of the site, tend to have lower survival rates compared to patients of other races. Multiple explanations have been put forth to explain this disparity, including delayed diagnosis, reduced access to care, and a propensity for more aggressive subtypes of common malignancies. With the inclusion of some of these potential mechanisms among the PL items, it is prudent to explore racial differences in responses to the DT and PL, as well as in factors that may underlie various measures of distress.

Widening the Therapeutic Window using an Implantable, Unidirectional LDR Brachytherapy Sheet as a Boost in Pancreatic Cancer

• Patients with borderline resectable pancreatic cancer are typically treated with neoadjuvant therapy including chemotherapy followed by chemoradiation with the goal of becoming surgical candidates. • Unfortunately, due to inflammatory changes after treatment the pre-operative imaging is not reliable in determining resectability and many patients still have concern for close or positive retroperitoneal margins given the proximity to major vasculature. • Post-operatively, an external beam RT (EBRT) boost is difficult given bowel constraints and difficulty in identifying the area at highest risk. • The purpose of this study is to demonstrate the ability of the LDR brachytherapy CivaSheet to deliver a focal high-dose boost, targeted to the area at highest risk in patients who received neoadjuvant chemoradiation.

The Long-Lasting Relationship of Distress on Radiation Oncology Specific Clinical Outcomes

Purpose: The diagnosis and treatment of cancer can have significant mental health ramifications. The National Comprehensive Cancer Network currently recommends using a distress screening tool to screen patients for distress and facilitate referrals to social service resources. Its association with radiation oncologyespecific clinical outcomes has remained relatively unexplored. Methods and materials: With institutional review board approval, National Comprehensive Cancer Network distress scores were collected for patients presenting to our institution for external beam radiation therapy during a 1-year period from 2015 to 2016. The association between distress scores (and associated problem list items and process-related outcomes) and radiation oncologyerelated outcomes, including inpatient admissions during treatment, missed treatment appointments, duration of time between consultation and treatment, and weight loss during treatment, was considered. Results: A total of 61 patients who received either definitive (49 patients) or palliative (12 patients) treatment at our institution and completed a screening questionnaire were included in this analysis. There was a significant association between an elevated distress score (7þ) and having an admission during treatment (36% vs 11%; P Z .04). Among the patients treated with definitive intent, missing at least 1 appointment (71% vs 26%; P Z .03) and having an admission during treatment (57% vs 10%; P Z .009) were significantly associated with our institutional definition of elevated distress. We found no correlation between distress score and weight loss during treatment or a prolonged time between initial consult and treatment start. Conclusions: High rates of distress are common for patients preparing to receive radiation therapy. These levels may affect treatment compliance and increase rates of hospital admissions. There remains equipoise in the best method to address distress in the oncology patient population. These results may raise awareness of the consequences of distress among radiation Meeting information: A previous version of this paper was presented at the American Society for Radiation Oncology Meeting on October 1, 2017. Sources of support: This work had no specific funding. Conflicts of interest: The authors have no conflicts of interest to disclose. * Corresponding author. Virginia Commonwealth University, Massey Cancer Center, Department of Radiation Oncology, Box 980058, Richmond, VA 23298. E-mail address: alexander.n.slade@vcuhealth.org (A.N. Slade). https://doi.org/10.1016/j.adro.2018.11.001 2452-1094/ 2018 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Advances in Radiation Oncology: AprileJune 2019 Distress and radiation oncology outcomes 355 oncology patients. Specific interventions to improve distress need further study, but we suggest a more proactive approach by radiation oncologists in addressing distress. 2018 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Introduction version; Fig 1) collected from 129 patients receiving In 1997, the National Comprehensive Cancer Network (NCCN) established a multidisciplinary panel to examine how to integrate psychosocial care into routine cancer care. Malignancies have long been known to disrupt a patient’s family, friendships, finances, and work life, and these disruptions are often difficult to recognize and address by providers. The NCCN Distress Thermometer is a tool that allows patients to score their level of distress on a scale of 0 to 10 (similar to the pain scale), with 0 being no distress and 10 being extreme distress. Physicians and others can use the tool to quickly identify patients with cancer who are experiencing distress and may benefit from intervention. The tool includes a problem list on which patients can answer additional questions to help pinpoint the source of distress and allow for more targeted interventions. When the Distress Thermometer was originally released, a score of 4 was sufficient to trigger additional questioning and possible referral to psychosocial services. This tool has provided a way for providers to quickly screen patients for distress and additional psychosocial concerns. Approximately a third of patients with cancer are estimated to experience a significant degree of distress, which varies by cancer site. High levels of distress on their own have been shown to be a poor prognostic factor, but elevated distress levels may precipitate or exacerbate symptoms, such as loss of appetite, difficulty concentrating, and sleeplessness. These and other symptoms may undermine patients’ ability to fight their own diseases. Some efforts have been made to correlate distress with specific cancer outcomes. One study found that high distress levels measured before and during radiation therapy (RT) prognostic with higher distress levels associated with decreased survival. This retrospective study explores the association between distress scores and radiation oncologyespecific outcomes. A secondary goal was to determine what factors could be contributing to worse outcomes in patients with high distress. Methods and Materials With institutional review board approval, we performed a retrospective review of our distress screening questionnaire and problem list (variation of the NCCN treatment at the Department of Radiation Oncology when they presented for their initial consultation between 2015 and 2016. Of these patients, 38 questionnaires had insufficient information to be included in the analysis (ie, did not report a distress score). An additional 30 patients were excluded because they did not ultimately receive RT at our institution (ie, it was received elsewhere or refused), were treated with brachytherapy as monotherapy (eg, for prostate cancer), or were treated for a benign condition (eg, Duputyren’s contracture). Of the 61 remaining patients, 49 were treated with definitive intent and 12 were treated with palliative (ie, noncurative) intent. We used Fisher’s exact test and t tests to evaluate the association between distress score and radiation oncologyespecific outcomes, including inpatient admissions during treatment, missed or canceled treatment appointments, duration of time between consultation and treatment, and weight loss during treatment. The policy established at our institution specifies that patients who report distress scores of 7 are considered high distress and trigger a social work consult. Therefore, we divided patients into 2 categories: low distress with scores of 6 and high distress with scores of 7 to 10. In addition to the ordinal 0-to-10 score, the NCCN scale also includes a problem list, which offers patients a yes/no response on 39 potential items that may have been problematic for the patient during the previous week. These items include practical problems, including child care and housing; family problems; emotional problems, such as depression; spiritual problems; and physical problems. Our institution makes minor modifications to this problem list (Fig 2). The overall number of reported problems was totaled according to their subsection of the problem list (ie, spiritual, family, practical, and physical). The breakdown of specific questions included in the categories is presented in Figure 2. Patients were given the option to check yes or no for each problem, but if a patient completed any of the problem list questions, missing answers were assumed to be no.

High-Dose Rate Salvage Interstitial Brachytherapy: A Case-Based Guide to the Treatment of Therapeutically Challenging Recurrent Vulvar Cancer

Vulvar cancer is a rare gynecological malignancy with incidence rates steadily increasing over the past 10 years. Despite aggressive treatment, recurrent disease is common. Vulvar cancer recurrence poses a significant therapeutic challenge as most patients have been previously treated with surgery and/or radiation limiting the options for additional treatment. There are no consensus guidelines for the treatment of recurrent disease. Current literature supports the use of salvage interstitial brachytherapy. However, the total sample size is small. The goal of this case report is to review the current literature and to provide a guide for the use of salvage interstitial brachytherapy for recurrent disease by describing, in detail, the techniques used to treat two patients with unique cases of vulvar cancer recurrences in women with advanced disease and multiple medical comorbidities.