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Background: Recent studies have suggested an association between radiation therapy (RT) of the left breast and increased incidence of coronary artery disease. However, the increased sparing afforded with modern RT may decrease long-term cardiac risk. The aims of our study were to evaluate the association between the RT and cardiac events in breast cancer patients who underwent contemporary RT and to examine whether breast arterial calcification (BAC) seen on mammogram predicts for cardiac events. Methods and Materials: In our observational, descriptive pilot study, 2,439 patients with breast cancer between 1986 and 2007 and a minimum of 3 years since completing RT were asked to complete a questionnaire regarding cardiac events since RT completion. The preoperative and follow-up mammograms were coded for presence/absence of BAC by an experienced radiologist blinded to questionnaire results. Cardiac events were compared between patients who received left- and right-sided adjuvant radiation. Results: At a mean follow-up of 7.5 years (range 3-24), 687 patients completed the questionnaire, with 602 eligible for analysis. Baseline characteristics (age, body mass index [BMI], surgery type, cardiovascular risk factors, and time since RT) were similar in patients who received left- versus right-sided RT. Hypertension before RT and during follow-up, baseline cardiovascular disease, age >50, BMI >30 kg/m2, and subsequent development of diabetes were significantly associated with posttreatment cardiac events. BACs were associated with cardiac events reported before breast cancer diagnosis; however, no association was found between left-sided breast RT or BAC and subsequent cardiac events. Conclusion: In a large single-institutional observational study, no association was found between left-sided breast RT or BAC and subsequent cardiac events. [ABSTRACT FROM AUTHOR]

Objective: To determine the dosimetric parameters predictive of acute gastrointestinal (GI) toxicity in anal cancer patients treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy. Methods: Fifty-eight anal cancer patients were treated with concurrent chemotherapy and IMRT. The bowel was delineated on the planning CT and included the intestinal cavity. Regression models with multiple independent predictors were used to test associations of clinical factors and dosimetric parameters with clinically significant GI toxicity (grade ≥3). Significant dosimetric factors were fitted to a normal tissue complication probability curve using a logit function and subsequently analyzed at multiple bowel volumes to determine the threshold for clinically significant GI toxicity. Results: Two patients (3.4%) experienced no acute GI toxicity, whereas 20 (34.5%) experienced grade 1 toxicity, 20 (34.5%) experienced grade 2, 16 (27.6%) experienced grade 3 and none experienced grade 4. Analysis showed that the volumes of bowel receiving 30 Gy (V30) and 40 Gy (V40) both correlated with clinically significant acute GI toxicity. In patients whose V30 was >310 cm3, the rate of clinically significant acute GI toxicity was 38.9%, compared to 9.1% if V30 was ≤310 cm3 (p = 0.016). If V40 was ≤70 cm3, the rate of acute grade ≥3 toxicity was 6.3%, versus 35.7% if V40 was >70 cm3 (p = 0.045). Conclusion: This analysis demonstrates that the bowel dosimetric parameters are associated with clinically significant acute GI toxicity when IMRT is used in the management of anal cancer patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Current National Comprehensive Cancer Network (NCCN) guidelines support systemic therapy based on mutational status in stage IV non-small cell lung cancer (NSCLC), with stereotactic body radiation therapy (SBRT) reserved for oligoprogression. We aimed to evaluate the cost-effectiveness of the routine addition of SBRT to upfront therapy in stage IV NSCLC by mutational subgroup., Materials and Methods: A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing SBRT plus maintenance therapy with maintenance therapy alone for oligometastatic NSCLC. Three hypothetical cohorts were analyzed: epidermal growth factor receptor or anaplastic lymphoma kinase mutation-positive, programmed death ligand-1 expressing, and mutation-negative group. Clinical parameters were obtained largely from clinical trial data, and cost data were based on 2018 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness to pay threshold of $100,000 per QALY gained., Results: SBRT plus maintenance therapy was not cost-effective at a $100,000/QALY gained threshold, assuming the same survival for both treatments, resulting in an incremental cost effectiveness ratio of $564,186 and $299,248 per QALY gained for the epidermal growth factor receptor or anaplastic lymphoma kinase positive and programmed death ligand-1 positive cohorts, respectively. Results were most sensitive to the cost of maintenance therapy. A large overall survival gain with SBRT could potentially result in upfront SBRT becoming cost-effective. For the mutation-negative cohort, upfront SBRT was nearly cost-effective, costing $128,424 per QALY gained., Conclusion: Adding SBRT to maintenance therapy is not a cost-effective strategy for oligometastatic NSCLC compared with maintenance therapy alone for mutation-positive groups. However, this should be validated via randomized trials.

Purpose: Rapid development of sophisticated modalities has challenged radiation oncologists to evaluate workflow and care delivery processes. Our study assesses treatment modality use and willingness to alter management with anticipated limitations in reimbursement and resources., Methods and Materials: A web-based survey was sent to 43 radiation oncologists in a National Cancer Institute-designated comprehensive cancer center network. The survey contained 7 clinical cases with various acceptable treatment options based on our institutional clinical pathways. Each case was presented in 3 modules with varying situations: (1) unlimited resources with current reimbursement, (2) restricted reimbursement (bundled payment), and (3) both restricted reimbursement and resources. Reimbursement rates were based on the 2013 Medicare fee schedule. Adoption of lower reimbursing options (LROs) was defined as the percentage of scenarios in which a respondent selected an LRO compared with baseline., Results: Forty-three physicians completed the survey, 11 (26%) at academic and 32 (74%) at community facilities. When bundled payment was imposed (module 1 vs 2), an increase in willingness to adopt LROs was observed (median 11.1%). When physicians were limited to both bundled payment and resource restriction, adoption of LROs was more pronounced (module 1 vs 3; median 22.2%, P < .01). There was a trend to selecting LROs between module 1 and 2 that reached significance when transitioning from module 1 to 3. A positive correlation between years in clinical practice and adoption of LROs was demonstrated (r(2) = 0.181, P<.01). This association remained significant when stratifying respondents by experience (≤25 vs >25 years, P = .02)., Conclusions: Radiation oncologists were more likely to choose lower reimbursing treatment options when both resource restriction and bundled payment were presented. Those with fewer years of clinical practice were less inclined to alter management, perhaps reflecting modern residency training. Future cost-utility analyses may help to better guide radiation oncologists in selection of LROs., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy., Methods and Materials: Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated high-dose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD2) with planned HRCTV doses of 75 to 85 Gy., Results: From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and cancer-specific survival rates were 91.6%, 81.8%, and 87.6%, respectively. Predictors of local failure included adenocarcinoma histology (P<.01) and clinical response at 3 months (P<.01). Among the adenocarcinoma subset, receiving HRCTV D90 EQD2 ≥84 Gy was associated with improved local control (2-year local control rate 100% vs 54.5%, P=.03). Grade 3 or greater gastrointestinal or genitourinary late toxicity occurred at a 2-year actuarial rate of 0.9%., Conclusions: This study constitutes one of the largest reported series of MRI-guided brachytherapy in North America, demonstrating excellent local control with acceptable morbidity. Dose escalation may be warranted when feasible for adenocarcinomas to offset the risk of local failure., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The tolerance and complication rates of the urethra are unknown for the interstitial high-dose-rate brachytherapy (HDR-BT) for vaginal cancer., Methods and Materials: Patients with vaginal cancer near/involving the urethra who were treated with HDR-BT between 2008 and 2011 were included. Patients received mean external beam dose of 48.0Gy followed by mean HDR-BT dose of 4.5Gy/fraction for five fractions. With CT-based planning, the urethra was contoured from the bladder neck to the meatus. Doses were converted to the biologically equivalent dose in 2Gy/fraction (EQD2)., Results: A total of 16 patients were included, and the EQD2D90 was 74.9Gy. The urethral volume was 1.31cm(3), and the EQD2 to 0.1 and 1cm(3) were 76.2 and 48.9Gy, respectively. Two of the 6 patients with urethral involvement developed urethral necrosis. The D90 for these 2 patients was 76.8Gy, and the urethral doses to 0.1 and 1cm(3) were 95.1 and 45.8, respectively. Those who developed severe urethral toxicity had a trend to urethral EQD2 (95.1Gy vs. 73.4Gy, p=0.1) and significantly higher dose per fraction of HDR-BT to 0.1cm(3) of the urethra (5.7Gy vs. 3.7Gy, p=0.02) when compared with those who did not develop severe urethral toxicity., Conclusions: This study is among the first to assess urethral dosimetry for patients treated with HDR-BT for vaginal cancer. Patients who received five fractions of higher than 5Gy/fraction to 0.1cm(3) of urethra (estimated EQD2 of 85Gy) are at increased risk of severe urethral toxicity., (Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: There is a suggestion that a dose-rate effect exists for the prostate-specific antigen (PSA) spike after brachytherapy. ¹³¹Cs is a newer radioisotope with a half-life of 9.7 days that is being used for prostate brachytherapy. There is no published data on the PSA spike with this radioisotope and the goal of this study was to quantify PSA spikes with ¹³¹Cs and compare it with published data for other isotopes., Methods and Materials: We have been maintaining a prospective database for all patients treated with ¹³¹Cs prostate brachytherapy at our institution. We selected patients for whom followup PSA was available for at least 24 months. The PSA spike was defined as an increase of 0.2 ng/mL, followed by a decline to prespike level., Results: One hundred twenty-three patients had monotherapy, whereas 32 had external beam radiation therapy followed by a brachytherapy boost. Median followup was 36 months and mean numbers of PSAs obtained were 7. Forty-six (29.7%) patients had a PSA spike. The mean time and duration for the PSA spike were 12.5 and 8.8 months, respectively. The mean magnitude of increase and mean PSA value at increase were 0.63 and 1.56 ng/mL, respectively., Conclusions: The incidence of a PSA spike in our series is consistent with reported numbers for other radioisotopes. The occurrence of the spike at 12.5 months appears to be at the early end of the spectrum reported for (125)I, but the duration and magnitude are similar to other radioisotopes., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Estrogen receptor (ER) status is a strong predictor of response to hormonal therapy in breast cancer patients. Presence of ER and level of expression have been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or aromatase inhibitors. Risk reduction is also known to occur in ER-negative, progesterone receptor (PR)-positive patients treated with hormonal therapy. Since the 1990s, immunohistochemistry has been the primary method for assessing hormone receptor status. Recently, as a component of its oncotype DX(®) assay, Genomic Health began reporting quantitative estrogen and PR results determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of an ongoing quality assurance program at our institution, we reviewed 464 breast cancer cases evaluated by both immunohistochemistry and oncotype DX(®) assay for estrogen and PR. We found good correlation for ER status between both assays (98.9% concordance), with immunohistochemistry being slightly more sensitive. Concordance for PR was 94.2% between immunohistochemistry and qRT-PCR with immunohistochemistry again more sensitive than RT-PCR. The results also showed linear correlation between immunohistochemistry H-scores and qRT-PCR expression values for ER (correlation coefficient of 0.579), and PR (correlation coefficient of 0.685). Due to the higher sensitivity of hormone receptor immunohistochemistry and additional advantages (ie preservation of morphology, less expensive, faster, more convenient), we conclude immunohistochemistry is preferable to qRT-PCR for determination of estrogen and PR expression.

Objectives: Three large randomized clinical trials have shown a survival benefit for patients treated with intraperitoneal (IP) compared with intravenous chemotherapy for advanced stage epithelial ovarian cancer (EOC). However, the use of IP chemotherapy in recurrent EOC is controversial. The purpose of this study was to determine outcomes, completion rates, and frequency of complications in patients with platinum-sensitive recurrent EOC treated with IP chemotherapy., Methods: A retrospective, single-institution analysis of women who received IP chemotherapy for recurrent EOC from January 2003 to April 2010 was conducted. Study patients were identified from the Tumor Registry and office records. Demographic factors, stage, histology, surgical findings, cytoreduction status, and subsequent therapies were abstracted. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier methods., Results: Fifty-six women who received IP chemotherapy for their first EOC recurrence were identified. The mean age of patients was 56.7 years (range, 40-79 y). Fifty-five patients (98.3%) had previously completed at least 6 cycles of intravenous chemotherapy. Of all patients, 87.5% were initially diagnosed with advanced stage disease (stage IIA-IV). All patients underwent secondary cytoreduction at the time of IP port placement. Moreover, 67.9% of patients were considered optimally cytoreduced (<1 cm residual disease) at the end of the secondary debulking surgery. Forty-two patients (75%) were able to successfully complete at least 6 cycles of IP chemotherapy. Reasons for noncompletion were disease progression, allergic reaction, renal failure, pain, severe nausea and vomiting, death, and patient refusal. Six patients (10.7%) developed port complications including pain around port site, port malfunction, and port erosion into small bowel. Median PFS since the initiation of IP chemotherapy was 10.5 months (95% confidence interval, 7.5-16.4 months) and median OS was 51 months (95% confidence interval, 40.8-61.1 months)., Conclusions: Intraperitoneal chemotherapy is a feasible option for patients with recurrent EOC, with high completion rates, low frequency of complications, and acceptable PFS and OS.

Background: Cancer antigen (CA)-125 is a biomarker widely used in the monitoring of response to chemotherapy in patients with epithelial ovarian cancer (EOC). We hypothesize that normalization of the CA-125 after the third cycle of chemotherapy is an independent prognostic indicator of prolonged progression-free survival (PFS) and overall survival (OS)., Methods: A retrospective analysis of patients with a diagnosis of advanced-stage (III-IV) EOC who were treated with cytoreductive surgery and adjuvant platinum-based chemotherapy from January 1999 to June 2009 was conducted. Patient demographics and the prognostic significance of CA-125 level above the discrimination value of 35 U/mL were assessed by univariate and multivariate analyses., Results: A total of 124 women met the study inclusion criteria. The median PFS for all patients with a CA-125 level of less than 35 U/mL (n = 72) after the third chemotherapy cycle was 18 months versus that of the patients with a CA-125 level of 35 U/mL or greater (n = 52) was 9 months (P < 0.0001). The median OS was 42 and 22 months, respectively (P < 0.0001). Optimal microscopically debulked patients with normalization of CA-125 after the third cycle did significantly better than those who did not normalize (PFS, 48 vs 8.3 months; OS, 59 vs 23.8 months; P < 0.0001). When patients with macroscopic disease and normalization of CA-125 after the third cycle were compared with those with CA-125 of 35 U/mL or greater, a significant difference in OS was seen between the 2 groups (47 vs 29 months, respectively; P < 0.0001). On multivariate analysis, only 2 variables were associated with poor prognosis: (1) the failure of CA-125 level to normalize after the third chemotherapy cycle (hazard ratio, 2.5; confidence interval, 1.3-4.6) and (2) the grade of the tumor (hazard ratio, 7.7; confidence interval, 1.6-37.6)., Conclusions: Although hypothesis generating at this point, normalization of CA-125 level after the third chemotherapy cycle is an independent predictor of survival for patients with advanced EOC regardless of debulking status. We would propose future trials that consider switching regimens in patients who do not normalize their CA-125 after the third cycle to see if such a switch can improve PFS and OS.