Outcomes for patients with head and neck sarcoma treated curatively with radiation therapy and surgery.

INTRODUCTION: Soft tissue sarcomas (STS) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS. METHODS: We performed a single-institution retrospective review of patients with non-metastatic STS of the H&N who were treated from 1968-2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVA) were conducted using Cox proportional hazards model. RESULTS: 192 pts had a median follow-up of 82 months. Tumors arose in the neck (n=50, 26%), paranasal sinuses (n=36, 19%), or face (n=23, 12%). Most patients were treated with post-operative RT (n=134, 70%). Post-op RT doses were higher (median 60Gy, pre-op 50Gy, p<0.001). Treatment sequence was not associated with LC (pre-op RT 78% (63-88), post-op RT 75% (66-82), p=0.48). On MVA, positive/uncertain margin was the only variable associated with LC (HR 2.54 (1.34-4.82), p=0.004). LC was significant on MVA (HR 4.48 (2.62-7.67), p<0.001) for DSS. Patients who received post-op RT were less likely to experience a major wound complication (MWC) (7.5% vs 22.4%, HR 0.28 (0.11-0.68), p=0.005). There was no difference in the rate of late toxicities between patients who received pre-op or post-op RT. CONCLUSIONS: H&N STS continues to have relatively poorer LC than STS of the trunk or extremities. We found LC to be associated with DSS. Timing of RT did not impact oncologic or long-term toxicity outcomes, however pre-op RT did increase the chance of developing a MWC.

SABR for Sarcoma Lung Metastases: Indications for Treatment and Guidance for Patient Selection.

PURPOSE: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases. METHODS AND MATERIALS: We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable analyses were conducted using the Cox proportional hazards model. RESULTS: We identified 70 patients with soft tissue sarcoma treated with SABR to 98 metastatic lung lesions. Local recurrence-free survival after SABR treatment was 83% at 2 years. On univariable analysis, receipt of comprehensive SABR to all sites of pulmonary metastatic disease at the time of treatment was associated with improved progression-free survival (PFS; hazard ratio [HR], 0.51 [0.29-0.88]; P = .02). On multivariable analysis, only having systemic disease controlled at the time of SABR predicted improved PFS (median PFS, 14 vs 4 months; HR, 0.37 [0.20-0.69]; P = .002) and overall survival (median overall survival, 51 vs 14 months; HR, 0.17 [0.08-0.35]; P < .0001). CONCLUSIONS: SABR provides durable long-term local control for sarcoma lung metastases. The most important predictor for improved outcomes was systemic disease control. Careful consideration of these factors should help guide decisions in a multidisciplinary setting to appropriately select the optimal candidates for SABR.

Comparing long-term sexual dysfunction across different uterine cancer treatment modalities.

INTRODUCTION: The objective of this study was to assess differences in long-term sexual and menopausal side effects after uterine cancer treatment among treatment modalities. METHODS AND MATERIALS: This is a cross-sectional study that examined women treated for uterine cancer from 2006-2018. Eligible women included those who underwent a hysterectomy/bilateral salpino-oophorectemy alone (HS), with brachytherapy (BT), or with external beam radiation therapy (EBRT). A noncancer cohort of women who underwent a hysterectomy/BSO for benign indications were also identified (non-CA). To compare outcomes, we utilized a shortened form of the female sexual function index (FSFI) and the menopause survey, which consists of 3 subscales: hot flashes, vaginal symptoms, and urinary symptoms. Demographic, comorbidity, and other treatment variables were collected. Survey totals were compared across cohorts using ANOVA tests and logistic regression. RESULTS: A total of 284 women completed the Menopause Survey (Non-CA 64, HS 60, BT 69, EBRT 91); 116 women reported sexual activity in the last 4 weeks and completed the FSFI (NC 32, HS 21, BT 31, EBRT 32). The mean FSFI score for the entire cohort was 11.4 (SD 4.16), which indicates poor sexual function. There was no significant difference between any cohort in the overall FSFI score (p = 0.708) or in any of the FSFI subscales (all p > 0.05). On univariate analysis, BT was associated with fewer menopausal hot flashes and vaginal symptoms compared to the non-CA cohort (p < 0.05), which did not persist on multivariable analysis. CONCLUSION: There was no significant difference in sexual dysfunction or menopausal symptoms in those treated for uterine cancer with or without adjuvant radiation. Most patients reported poor sexual function.

Association Between Symptom Burden and Early Lymphatic Abnormalities After Regional Nodal Irradiation for Breast Cancer.

PURPOSE: Dermal backflow visualized on near-infrared fluorescence lymphatic imaging (NIRF-LI) signals preclinical lymphedema that precedes the development of volumetrically defined lymphedema. We sought to evaluate whether dermal backflow correlates with patient-reported lymphedema outcomes (PRLO) surveys in breast cancer patients treated with regional nodal irradiation (RNI). METHODS AND MATERIALS: Patients with breast cancer planned for axillary dissection and RNI prospectively underwent perometry, NIRF-LI, and PRLOs (the Lymphedema Symptom Intensity and Distress Survey [LSIDS] and QuickDASH) at baseline, after surgery, and at 6, 12, and 18 months after radiation. Clinical lymphedema was defined as an arm volume increase ≥5% over baseline. Trends over time were assessed using analysis of variance testing. The association between survey responses and both dermal backflow and lymphedema was assessed using a linear mixed-effects model. RESULTS: Sixty participants completed at least 2 sets of measurements and surveys and were eligible for analysis. Fifty-four percent of patients had cT3-T4 disease, 53% cN3 disease, and 75% had a body mass index >25. Dermal backflow and clinical lymphedema increased from 10% to 85% and from 0% to 40%, respectively, from baseline to 18 months. In the adjusted model, soft tissue sensation, neurologic sensation, and functional LSIDS subscale scores were associated with presence of dermal backflow (all P < .05). Both dermal backflow and lymphedema were associated with QuickDASH score (P < .05). CONCLUSIONS: In this high-risk cohort, we found highly prevalent early signs of lymphedema, with increased symptom burden from baseline. Presence of dermal backflow correlated with PRLO measures, highlighting a potential NIRF-LI use to identify patients for early intervention trials after RNI.

Outcomes after definitive treatment for cutaneous angiosarcomas of the face and scalp: Reevaluating the role of surgery and radiation therapy.

INTRODUCTION: We investigated outcomes and prognostic factors for patients treated for cutaneous angiosarcoma (CA). METHODS: We conducted a retrospective review of patients treated for CA of the face and scalp from 1962 to 2019. All received definitive treatment with surgery, radiation (RT), or a combination (S-XRT). The Kaplan-Meier method was used to estimate outcomes. Multivariable analyses were conducted using the Cox proportional hazards model. RESULTS: For the 143 patients evaluated median follow-up was 33 months. Five-year LC was 51% and worse in patients with tumors >5 cm, multifocal tumors, those treated pre-2000, and with single modality therapy (SMT). These remained associated with worse LC on multivariable analysis. The 5-year disease-specific survival (DSS) for the cohort was 56%. Tumor size >5 cm, non-scalp primary site, treatment pre-2000, and SMT were associated with worse DSS. CONCLUSION: Large or multifocal tumors are negative prognostic factors in patients with head and neck CA. S-XRT improved outcomes.

Definitive local therapy for T4 prostate cancer associated with improved local control and survival.

OBJECTIVES: To evaluate patients with clinical (c)T4 prostate cancer (PCa), which represent both a heterogenous and understudied population, who often present with locally advanced disease and obstructive symptoms causing significant morbidity and mortality. We analysed whether receiving definitive local therapy influenced symptomatic and oncological outcomes. METHODS: Retrospective analysis of 154 patients with cT4 PCa treated at a single institution in 1996-2020. Systemic therapy with or without local treatment (surgery, radiotherapy [RT], or both). Uni- and multivariate analyses of associations between clinicopathological features (including obstructive symptoms) and receipt of local therapy on overall survival (OS) and disease control were done with Cox regression. RESULTS: The median follow-up time was 5.9 years. Most patients had adenocarcinoma (88%), Gleason score 9-10 (77%), and median baseline prostate-specific antigen (PSA) of 20 ng/mL; most (54%) had metastatic cT4N0-1M1 disease; 24% regionally advanced cT4N1M0, and 22% localised cT4N0M0. Local therapies were RT (n = 44), surgery (n = 28), or both (n = nine). Local therapy was associated with improved OS (hazard ratio [HR] 0.3, P < 0.001), longer freedom from local recurrence (HR 0.39, P = 0.002), less local progression (HR 0.41, P = 0.02), fewer obstructive symptoms with progression (HR 0.31, P = 0.01), and less death from local disease (HR 0.25, P = 0.002). On multivariate, local therapy was associated with improved survival (HR 0.58, P = 0.02), and metastatic disease (HR 2.93, P < 0.001) or high-risk pathology (HR 2.05, P = 0.03) was associated with worse survival. CONCLUSION: Definitive local therapy for cT4 PCa was associated with improved symptomatic outcomes and survival even among men with metastatic disease. Pending prospective evaluation, these findings support definitive treatment with local therapy for cT4 disease in select cases.

Effect of Quality of Life on Radiation Adherence for Patients With Cervical Cancer in an Urban Safety Net Health System.

PURPOSE: Outcomes for patients undergoing chemoradiation for cervical cancer are dependent on adherence to radiation therapy (RT). In other diseases, quality of life (QoL) is associated with treatment adherence, but the association between QoL and RT adherence for patients with cervical cancer remains unclear. METHODS AND MATERIALS: This prospective study included patients undergoing RT for cervical cancer from 2017 to 2021 at an urban safety net hospital. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 was used to assess QoL based on 5 subscales (physical, functional, social and emotional, and cervical-cancer specific). The survey was administered at radiation consult, then weekly during RT and at follow-up. Patient information was abstracted from the medical record. Radiation nonadherence was defined as missing ≥2 days of external beam RT. The Functional Assessment of Cancer Therapy-Cervical Cancer Version 4 total and subscale scores were compared between adherent and nonadherent patients. Multivariable logistic regression was performed to control for confounding variables. RESULTS: Ninety-three patients were enrolled, completing 522 surveys. Median age at diagnosis was 46 years (interquartile range, 40-51); 76% of patients were Hispanic, and 12% were Black. Only 30% of patients were nonadherent with RT. A psychiatric comorbidity (P = .012) and symptomatic presentation (P = .027) were associated with decreased adherence. Baseline total QoL was higher in treatment-adherent than in nonadherent patients (median, 124.86; range, 48-160; 108.9, 46-150; P = .01). Higher baseline functional and physical subscale scores were associated with adherence (P < .05). Change from baseline to lowest score during treatment in the emotional subscale was also associated with patient adherence (P < .05). In multivariable analysis, higher baseline physical score, baseline total score, and change in emotional subscale score were associated with adherence (P < .05). CONCLUSIONS: Poor QoL during chemoradiation for cervical cancer is associated with missed treatments. Physician assessment of a patient's well-being while they are undergoing RT is of utmost importance to improve adherence to treatment.

Impact of treatment modality on pelvic floor dysfunction among uterine cancer survivors.

OBJECTIVE: Pelvic floor dysfunction is a common adverse effect of uterine cancer treatment. In this study we compared patient-reported outcomes regarding pelvic floor dysfunction among uterine cancer survivors after hysterectomy and bilateral salpingo-oophorectomy, surgery and brachytherapy, or surgery and external beam radiotherapy with or without brachytherapy versus women who had a hysterectomy for benign indications. METHODS: We used the validated 20-item Pelvic Floor Distress Inventory to assess lower urinary distress, colorectal distress, and pelvic organ prolapse dysfunction in each treatment group. Pelvic floor dysfunction-related quality of life in these domains was compared across treatment modalities using the Pelvic Floor Impact Questionnaire-7. Treatment type, body mass index, comorbidities, and number of vaginal births were obtained from medical records. A zero-inflated negative binomial regression model was used to assess the association of treatment regimens and covariates relative to the non-cancer cohort. RESULTS: A total of 309 surveys were analyzed. The median age of the patients at surgery was 58 years (range 20-87) and the median age at survey completion was 66 years (range 34-92). Most participants reported experiencing at least one symptom of pelvic floor dysfunction (76% by Pelvic Floor Distress Inventory-2). The type of treatment had no effect on overall pelvic floor dysfunction on multivariate analysis (all p>0.05). Worse urinary-related symptoms were associated with higher body mass index at surgery (OR 1.41), higher age at time of survey (OR 1.07), and higher numbers of vaginal births (OR 1.43) (all p<0.05). CONCLUSIONS: Overall, pelvic floor dysfunction did not significantly vary by treatment modality. Our findings suggest complex interactions among age, body mass index, and parity as to how uterine cancer treatment affects pelvic floor quality of life, which should be considered in the choice of treatment strategy and patient counseling.

Impact of hematologic toxicities during concurrent chemoradiation for cervical cancer.

OBJECTIVE: To evaluate the prognostic significance of hematological toxicities during cervical cancer treatment. METHODS: Patients treated for cervical carcinoma with definitive chemoradiation were identified. Toxicities were assessed during weeks 1 to 6 of concurrent external beam radiation and chemotherapy. Outcomes were analyzed using Cox regression analysis. RESULTS: One hundred twenty-one patients with Federation of Gynecology and Obstetrics stage I-III disease were eligible for analysis. Median age at diagnosis was 45 years (interquartile range, 40-52) with median follow-up time of 34 months (95% confidence interval, 30.8-37.2). All patients experienced some grade of hematologic toxicity. The most common grade 3+ toxicities were low absolute lymphocyte count (n=115, 95%), low white blood cell count (n=21, 17%), and anemia (n=11, 9%). The most common grade 4 toxicity was lymphopenia, experienced by 36% of patients (n=44). Grade 4 lymphopenia was associated with reduced overall survival (hazard ratio [HR], 4.5; P=0.005), progression-free survival (HR, 3.4; P=0.001), and local control (HR, 4.1; P=0.047). Anemia grade 3, 4 was also associated with reduced overall survival (HR, 4.1; P=0.014). After controlling for disease and treatment variables, grade 4 lymphopenia remained significantly associated with reduced overall survival (HR, 9.85; P=0.007). The association with grade 4 lymphopenia only remained significant in women of Hispanic ethnicity. CONCLUSION: Severe lymphopenia was associated with reduced overall survival and progression-free survival in Hispanic women undergoing definitive chemoradiation for cervical cancer, but not associated with outcomes in non-Hispanic women.

The association between protease inhibitors and anal cancer outcomes in veterans living with HIV treated with definitive chemoradiation: a retrospective study.

BACKGROUND: The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer. METHODS: Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression. RESULTS: A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratio p-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p < 0.01). CONCLUSION: The use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.

Hitting a Moving Target: Successful Management of Diffuse Large B-cell Lymphoma Involving the Mesentery With Volumetric Image-guided Intensity Modulated Radiation Therapy.

INTRODUCTION: We report successful treatment of mesenteric diffuse large B-cell lymphoma (DLBCL) using localized involved site radiation therapy (ISRT), intensity modulated radiation therapy (IMRT), and daily computed tomography (CT)-image guidance. PATIENTS AND METHODS: Patients with mesenteric DLBCL treated with RT between 2011 and 2017 were reviewed. Clinical and treatment characteristics were analyzed for an association with local control, progression-free survival (PFS), and overall survival. RESULTS: Twenty-three patients were eligible. At diagnosis, the median age was 52 years (range, 38-76 years), and 57% (n = 13) had stage I/II DLBCL. All patients received frontline chemotherapy (ChT) (R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone], n = 19; dose-adjusted R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin], n = 4) with median 6 cycles. Prior to RT, salvage ChT for refractory DLBCL was given to 43% (n = 10) and autologous stem cell transplantation was administered in 13% (n = 3). At the time of RT, positron emission tomography-CT revealed 5-point scale of 1 to 3 (48%; n = 11), 4 (9%; n = 2), and 5 (44%; n = 10). All patients received IMRT, daily CT imaging, and ISRT. The median RT dose was 40 Gy (range, 16.2-49.4 Gy). Relapse or progression occurred in 22% (n = 5). At a median follow-up of 37 months, the 3-year local control, PFS, and overall survival rates were 80%, 75%, and 96%, respectively. Among patients treated with RT after complete metabolic response to frontline ChT (n = 8), the 3-year PFS was 100%, compared with 61% for patients with a history of chemorefractory DLBCL (n = 15; P = .055). Four of the 5 relapses occurred in patients with 5-point scale of 5 prior to RT (P = .127). CONCLUSION: Mesenteric involvement of DLBCL can be successfully targeted with localized ISRT fields using IMRT and daily CT-image guidance.

Inversely and adaptively planned interstitial brachytherapy: A single implant approach.

OBJECTIVE: To evaluate the efficacy, feasibility and safety of image-based, inversely and adaptively planned high-dose rate interstitial brachytherapy (HDR-ISBT) to treat advanced primary or recurrent gynecologic malignancy in a single implant, three-consecutive-day regimen. METHODS: Clinical demographics and outcome data were abstracted from all patients with primary and recurrent gynecologic malignancies who received HDR-ISBT boost from 2014 to 2017. Treatment consisted of a single implant (~7 Gy × 4 fractions) of interstitial needles using the Syed-Neblett template over a three-day hospital admission. CT-based (3D) simulation with inverse and adaptive planning was utilized for each fraction. MR prior to and MR immediately after external beam therapy were fused for HDR-ISBT target delineation. RESULTS: Forty women with an overall median follow-up of 18 months (range: 6-54 months) received an HDR-ISBT boost. Of the 30 primary cases (83% cervix, 10% vaginal, 7% uterine), 44% had organ invasion (bladder, rectal or both) on MRI. Median coverage and dose are reported (V100: 98%, HR-CTV EQD2: 85.1 Gy, D90: 92 Gy). A significant association existed between rectal doses exceeding GEC-ESTRO recommendations (D2cc < 75 Gy) and the development of grade 3 gastrointestinal toxicity with a relative risk of 1.4 [1.1-1.8] (p = .046). Actuarial two-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81%, 81% and 64%, respectively. CONCLUSIONS: A four fraction, inversely and adaptively planned, single-implant approach of image-based HDR-ISBT provides excellent coverage, minimal toxicity and effective local control in patients with advanced and recurrent disease.

Stereotactic Body Radiation Therapy for Prostate Cancer: An Institutional Experience Using MRI-guided Treatment Planning.

With 222,500 new cases estimated for 2017, prostate cancer makes up approximately 10% of all new cancer diagnoses in the United States and is the third most common cancer after breast and lung cancer. In 2013, the American Society of Radiation Oncology (ASTRO) policy model recognized that stereotactic body radiation therapy (SBRT) may be used as an alternative to standard treatment modalities, i.e. intensity modulated radiation therapy (IMRT), to treat prostate cancer. In this study, we report outcomes for a cohort of 30 patients with prostate cancer treated with SBRT at our institution. We also describe, in detail, the technical aspects of SBRT planning and delivery for these patients, specifically the use of MRI in determining treatment volumes and detecting gross lesions. After institutional review board (IRB) approval, a retrospective analysis was done of 30 males with the diagnosis of prostate cancer treated in the Department of Radiation Oncology at the Baylor College of Medicine between January 2011 and June 2016. All patients received image-guided SBRT. Treatment planning was performed using a non-contrast computed tomography (CT) scan as well as a contrast thin-slice open MRI with the patient in the treatment position. Patient comparisons were done using the Mann-Whitney U, Fishers Exact, and Kaplan-Meier tests. Thirty patients were treated between January 2011 and June 2016. Twenty-six had follow-up data available and were included in the analysis. Median follow-up was 32 months (range 2-72 months). Mean and median ages at diagnosis were both 68.5 years. A total of 64% of the patients had foci on magnetic resonance imaging (MRI) or a palpable nodule on an exam. The median prostate-specific antigen (PSA) at diagnosis was 7.35 ng/mL (range 2.8-13), and the median PSA nadir after treatment was 0.4 ng/mL (range 0.01-4.5). The biochemical disease-free recurrence rate per Phoenix definition was 96%, with only one patient experiencing a biochemical recurrence four years after treatment. The patient with a recurrence was T2c, high-intermediate risk with a Gleason score of 7(3+4). He had a focus visible on MRI. Overall survival was 96%, with the only patient death unrelated to his prostate cancer. There was no statistical significance associated with recurrence and nodule on MRI (p=0.318), T-stage (p=0.222), Gleason score (p=0.890), risk group (p=0.654), age (p=0.692), or race (p=0.509). There were no grade three or four acute or long-term toxicities. SBRT of the prostate is an effective method for treating prostate cancer. We saw excellent PSA control and minimal acute or long-term toxicities after a median of three years of follow-up.