A prospective clinical and transcriptomic feasibility study of oral-only hormonal therapy with radiation for unfavorable prostate cancer in men 70 years of age and older or with comorbidity.

BACKGROUND: Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression. METHODS: Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment. RESULTS: Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling. CONCLUSIONS: For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.

The effect of treatment time in locally advanced cervical cancer in the era of concurrent chemoradiotherapy.

BACKGROUND: This study sought to determine if treatment time impacts pelvic failure (PF), distant failure (DF), or disease-specific mortality (DSM) in patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: A retrospective review was performed of 113 consecutive eligible patients with stage IB2 to IIIB cervical cancer. All patients received whole-pelvis radiation with concurrent chemotherapy and consolidative intracavitary brachytherapy (BT) to the cervix, followed by an external beam parametrial boost when appropriate. The effect of treatment time on PF, DF, and DSM was examined with univariate and multivariate analyses. Characteristics of patients with and without treatment prolongation were compared to explore reasons for treatment prolongation. RESULTS: The median time to completion of BT was 60 days, and the median time to complete all RT was 68 days. The 3-year cumulative incidence of PF, DF, and DSM were 18%, 23%, and 26%, respectively. On multivariate analysis, time to completion of BT >56 days was associated with increased PF (hazard ratio, 3.8; 95% confidence interval, 1.2-16; P = .02). The 3-year PF for >56 days versus ≤56 days was 26% versus 9% (P = .04). Treatment time was not associated with DF or DSM. Treatment prolongation was found to be associated with delay in starting BT and higher incidence of acute grade 3/4 toxicities. CONCLUSIONS: In the setting of CCRT, treatment time >56 days is detrimental to pelvic control but is not associated with an increase in DF or DSM. To maximize pelvic control, we recommend completing BT in 8 weeks or less.

Improving the Pediatric Patient Experience During Radiation Therapy-A Children's Oncology Group Study.

PURPOSE: Treatment with radiation therapy (RT) can cause anxiety and distress for pediatric patients and their families. Radiation oncology teams have developed strategies to reduce the negative psychological impact. This survey study aimed to characterize these methods. METHODS AND MATERIALS: A 37-item questionnaire was sent to all radiation oncology members of the Children's Oncology Group to explore strategies to improve the pediatric patient experience. The Wilcoxon rank-sum test was used to assess factors associated with use of anesthesia for older children. RESULTS: Surveys were completed by 106 individuals from 84/210 institutions (40%). Respondents included 89 radiation oncologists and 17 supportive staff. Sixty-one percent of centers treated ≤50 children per year. Respondents described heterogenous interventions. The median age at which most children no longer required anesthesia was 6 years (range: ≤3 years to ≥8 years). Routine anesthesia use at an older age was associated with physicians' lack of awareness of these strategies (P = .04) and <10 years of pediatric radiation oncology experience (P = .04). Fifty-two percent of respondents reported anesthesia use added >45 minutes in the radiation oncology department daily. Twenty-six percent of respondents planned to implement new strategies, with 65% focusing on video-based distraction therapy and/or augmented reality/virtual reality. CONCLUSIONS: Many strategies are used to improve children's experience during RT. Lack of awareness of these interventions is a barrier to their implementation and is associated with increased anesthesia use. This study aims to disseminate these methods with the goal of raising awareness, facilitating implementation, and, ultimately, improving the experience of pediatric cancer patients and their caregivers.

Application of 21-gene recurrence score results and ASTRO suitability criteria in breast cancer patients treated with intraoperative radiation therapy (IORT).

BACKGROUND: American Society for Radiation Oncology (ASTRO) suitability criteria for accelerated partial breast irradiation (APBI) and the 21-gene recurrence score (RS) were evaluated for prognostic and predictive benefit in IORT patients. METHODS: Outcomes of 184 patients completing IRB approved IORT protocol were retrospectively reviewed. Data included demographics, histopathology, RS, adjuvant therapy, locoregional (LRR) and distant recurrences (DR), and breast cancer-specific survival. RESULTS: There were 10 (5.4%) breast cancer recurrences, including one breast cancer-specific death. All 184 patients were classified by ASTRO suitability criteria (suitable: 64% (5 LRR), cautionary: 30% (3 LRR), unsuitable: 6.0% (1 LRR, 1 DR leading to death). RS were available in 114 estrogen receptor positive patients (<11: 22% (1 LRR), 11-25: 63% (1 LRR), 26-30: 9%, >30: 6%). Mean follow-up was 55 months. CONCLUSIONS: ASTRO suitability criteria for APBI and RS were useful in making prognostic and therapeutic recommendations for patients considering IORT.

Locoregional recurrence after mastectomy: incidence and outcomes.

BACKGROUND: Locoregional recurrences (LRR) after mastectomy may be ominous events, but incidence and outcomes data are limited by heterogeneous study populations and the time period studied. We sought to evaluate the rate of LRR at a single institution in the era of multimodality therapy, identify predictors for isolated LRR, and examine treatment strategies and outcomes of postmastectomy patients with isolated LRR. STUDY DESIGN: In a prospective database, we identified 1,057 patients who underwent mastectomy for invasive cancer at Memorial Sloan-Kettering Cancer Center from 1995 to 1999. Predictive factors for isolated LRR were determined by univariate and multivariate analyses. Treatments and outcomes of patients with isolated LRR were reviewed. All patients with at least 2 years of followup were included. Median followup was 6 years. RESULTS: Overall, LRR developed in 93 of 1,057 (8.8%) patients. Thirty-four (3.2%) had synchronous distant metastases. Distant recurrences developed in thirty-one (2.9%) during the followup period (median followup, 6 years). Twenty-eight patients with LRR (2.6%) remained free of distant disease during the study period. Multivariate analysis showed age less than 35 years, lymphovascular invasion, and multicentricity as major predictors for isolated LRR. In the 28 patients with isolated LRR, 24 had recurrence in the chest wall, 2 in the axilla, and 2 in more than 1 local site. Seventy-eight percent (22 of 28) of patients were rendered disease free with surgery (15 of 22), radiotherapy (13 of 22), chemotherapy (6 of 22), or hormones (9 of 22). CONCLUSIONS: Despite widespread use of adjuvant therapies during the study period, we found an LRR rate after mastectomy of 9%. But for patients presenting with LRR without evidence of distant disease, aggressive multimodality therapy is warranted because many of these patients can be rendered disease free.

Hypofractionated radiotherapy does not increase acute toxicity in large-breasted women: results from a prospectively collected series.

BACKGROUND AND PURPOSE: To compare the acute toxicity of hypofractionated whole breast radiotherapy (HypoRT) to conventionally fractionated radiotherapy (ConvRT) in large-breasted women with early stage disease. MATERIALS AND METHODS: Women with breast volume>1500 cm, body mass index>30 kg/m, or separation>25 cm treated with HypoRT or ConvRT from 2005 through 2010 were identified from a prospective database and included in the analysis. Acute toxicity was scored for each treated breast. RESULTS: Ninety-two patients were treated to 96 breasts. The median body mass index was 33 kg/m and median breast volume was 1932 cm for the ConvRT group compared with 32.4 kg/m and 1825 cm for the HypoRT group. Maximum acute skin toxicity consisted of focal moist desquamation in 26% and 11% of the ConvRT and HypoRT patients, respectively (P=0.002). Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (P=0.01). Among those with a breast volume >2500 cm, focal moist desquamation occurred in 40.7% (11/27) compared with 11.1% (7/63) in patients with breast volume <2500 cm (P=0.002). CONCLUSIONS: Among obese and large-breasted women, there was no increase in acute skin toxicity with the use of HypoRT. HypoRT should be considered in obese and large-breasted women when advanced planning techniques are used.

A prospective study of the utility of magnetic resonance imaging in determining candidacy for partial breast irradiation.

PURPOSE: Retrospective data have demonstrated that breast magnetic resonance imaging (MRI) may change a patient's eligibility for partial breast irradiation (PBI) by identifying multicentric, multifocal, or contralateral disease. The objective of the current study was to prospectively determine the frequency with which MRI identifies occult disease and to establish clinical factors associated with a higher likelihood of MRI prompting changes in PBI eligibility. METHODS AND MATERIALS: At The University of Chicago, women with breast cancer uniformly undergo MRI in addition to mammography and ultrasonography. From June 2009 through May 2011, all patients were screened prospectively in a multidisciplinary conference for PBI eligibility based on standard imaging, and the impact of MRI on PBI eligibility according to National Surgical Adjuvant Breast and Bowel Project protocol B-39/Radiation Therapy Oncology Group protocol 0413 entry criteria was recorded. Univariable analysis was performed using clinical characteristics in both the prospective cohort and in a separate cohort of retrospectively identified patients. Pooled analysis was used to derive a scoring index predictive of the risk that MRI would identify additional disease. RESULTS: A total of 521 patients were screened for PBI eligibility, and 124 (23.8%) patients were deemed eligible for PBI based on standard imaging. MRI findings changed PBI eligibility in 12.9% of patients. In the pooled univariable analysis, tumor size ≥ 2 cm on mammography or ultrasonography (P=.02), age <50 years (P=.01), invasive lobular histology (P=.01), and HER-2/neu amplification (P=.01) were associated with a higher likelihood of MRI changing PBI eligibility. A predictive score was generated by summing the number of significant risk factors. Patients with a score of 0, 1, 2, and 3 had changes to eligibility based on MRI findings in 2.8%, 13.2%, 38.1%, and 100%, respectively (P<.0001). CONCLUSIONS: MRI identified additional disease in a significant number of patients eligible for PBI, based on standard imaging. Clinical characteristics may be useful in directing implementation of MRI in the staging of PBI candidates.

Feasibility and acute toxicity of hypofractionated radiation in large-breasted patients.

PURPOSE: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. METHODS AND MATERIALS: A review was conducted of all patients consecutively treated with HypoRT at the University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a "field-in-field" technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. RESULTS: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m(2). Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). CONCLUSIONS: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women with a PTV volume >2,500 mL.

Utility of breast magnetic resonance imaging in patients with occult primary breast cancer.

BACKGROUND: Although carcinoma presenting as axillary metastases is assumed to be due to breast cancer, identification of the primary lesion may prove problematic. We investigated the ability of breast magnetic resonance imaging (MRI) to identify the primary tumor, thereby confirming the diagnosis and broadening treatment options. METHODS: From 1995 to 2001, 69 patients at our institution presented with occult primary breast cancer. All patients had negative breast examinations and mammograms and underwent breast MRI. RESULTS: Of 69 patients, 55 had axillary adenopathy without evidence of distant disease (stage II); 14 had stage IV disease. In patients with stage II disease, MRI revealed suspicious lesions in 76% (42 of 55). In 62% (26 of 42), the MRI finding proved to be the occult primary tumor. Of these, 58% (15 of 26) were candidates for breast conservation. MRI did not identify the primary tumor in 25 women; 12 underwent mastectomy. Cancer was found in 33% (4 of 12) of these. Thirteen patients were treated with primary breast irradiation; three were lost to follow-up, one developed distant disease, and nine were without evidence of disease with a median follow-up of 4.5 years. In women with stage IV disease, MRI identified the primary tumor in 5 of 9 patients with regional adenopathy and 2 of 5 patients with distant disease (overall 50%; 7 of 14). MRI identified the primary tumor in women with both mammographically dense (19 of 44; 43%) and less dense (10 of 20; 50%) breasts. CONCLUSIONS: Breast MRI detects mammographically occult cancer in half of women with axillary metastases, regardless of breast density. MRI is a powerful tool for stage II and stage IV patients with occult primary breast cancer.