Defining the role of intensity modulation in electron conformal therapy for the treatment of head and neck cancer.

Bolus electron conformal therapy (BECT) in the treatment of cancers of the head and neck is often limited by an inability to reduce dosimetric hot spots resulting from surface irregularity or tissue heterogeneity. We examined the potential benefits of using intensity modulation for electron therapy (IM-BECT) to reduce hotspots in patients undergoing electron beam therapy for superficial cancers of the head and neck (HN). Twenty patients with HN cancer previously treated with BECT were identified. Each case included the treatment targets and a primary organ at risk (OAR) that were defined by the radiation oncologist. A target +2 cm rind structure was created for analysis of the dose deposition in areas surrounding the target volume as a measure of conformality. Each patient plan was transferred into the novel IM-BECT planning software and each case was recomputed as per the original parameters. Next, each case was replanned with the inclusion of intensity modulation, as well as a new custom conformal bolus that was redesigned for optimized range compensation when paired with an intensity modulator. The plans were then normalized to prescription dose and compared for target coverage/dose and OAR dose. For patients who had a hotspot of 125% or greater, the hotspot was on average reduced by 13.1% with IM-BECT. For IM-BECT, the average primary OAR means dose and target+2cm rind mean dose increased slightly by 10.6% and 6.4%, respectively (primary OAR mean [p = 0.0001], and Target+2cm rind mean [p = 0.0001], paired t-test). IM-BECT is an effective method of reducing hotspots in patients with superficial HN cancer. Improvements came at the expense of slight increases in dose to the underlying tissues. This retrospective planning study represents the first example of IM-BECT to actual HN patient cases. Expanding the role of IM-BECT in other disease sites could potentially compared to conventional BECT.

Advancing the Role of Proton Therapy for Spine Metastases Through Diagnostic Scan-Based Planning.

Purpose: Many patients with metastatic cancer live years beyond diagnosis, and there remains a need to improve the therapeutic ratio of metastasis-directed radiation for these patients. This study aimed to assess a process for delivering cost-effective palliative proton therapy to the spine using diagnostic scan-based planning (DSBP) and prefabricated treatment delivery devices. Materials and Methods: We designed and characterized a reusable proton aperture system that adjusts to multiple lengths for spine treatment. Next, we retrospectively identified 10 patients scan treated with thoracic proton therapy who also had a diagnostic computed tomography within 4 months of simulation. We contoured a T6-T9 target volume on both the diagnostic scans (DS) and simulation scans (SS). Using the aperture system, we generated proton plans on the DS using a posterior-anterior beam with no custom range compensator to treat T6-T9 to 8 Gy × 1. Plans were transferred to the SS to compare coverage and normal tissue doses, followed by robustness analysis. Finally, we compared normal tissue doses and costs between proton and photon plans. Results were compared using the Wilcoxon signed-rank test. Results: Median D95% on the DS plans was 101% (range, 100%-102%) of the prescription dose. Median Dmax was 107% (range, 105%-108%). When transferred to SS, coverage and hot spots remained acceptable for all cases. Heart and esophagus doses did not vary between the DS and SS proton plans (P >.2). Robustness analysis with 5 mm X/Y/Z shifts showed acceptable coverage (D95% > 98%) for all cases. Compared with the proton plans, the mean heart dose was higher for both anterior-posterior/posterior-anterior and volumetric modulated arc therapy plans (P < .01). Cost for proton DSBP was comparable to more commonly used photon regimens. Conclusion: Proton DSBP is technically feasible and robust, with superior sparing of the heart compared with photons. Eliminating simulation and custom devices increases the value of this approach in carefully selected patients.

Differences in Time Burden across Local Therapy Strategies for Early-stage Breast Cancer.

"Time burden" (time required during treatment) is relevant when choosing a local therapy option for early-stage breast cancer but has not been rigorously studied. We compared the time burden for three common local therapies for breast cancer: (1) lumpectomy plus whole-breast irradiation (Lump+WBI), (2) mastectomy without radiation or reconstruction (Mast alone), and (3) mastectomy without radiation but with reconstruction (Mast+Recon). METHODS: Using the MarketScan database, we identified 35,406 breast cancer patients treated from 2000 to 2011 with these local therapies. We quantified the total time burden as the sum of inpatient days (inpatient-days), outpatient days excluding radiation fractions (outpatient-days), and radiation fractions (radiation-days) in the first two years postdiagnosis. Multivariable regression evaluated the effect of local therapy on inpatient-days and outpatient-days adjusted for patient and treatment covariates. RESULTS: Adjusted mean number of inpatient-days was 1.0 for Lump+WBI, 2.0 for Mast alone, and 3.1 for Mast+Recon (P < 0.001). Adjusted mean number of outpatient-days was 42.9 for Lump+WBI, 42.2 for Mast alone, and 45.8 for Mast+Recon (P < 0.001). The mean number of radiation-days for Lump+WBI was 32.4. Compared with Mast+Recon (48.9 days), total adjusted time burden was 4.7 days shorter for Mast alone (44.2 days) and 27.4 days longer for Lump+WBI (76.3 days). However, use of a 15 fraction WBI regimen would reduce the time burden differential between Lump+WBI and Mast+Recon to just 10.0 days. CONCLUSIONS: Although Mast+Recon confers the highest inpatient and outpatient time burden, Lump+WBI carries the highest total time burden. Increased use of hypofractionation will reduce the total time burden for Lump+WBI.

Whole brain radiotherapy with hippocampal sparing using Varian HyperArc.

The purpose of this work was to evaluate using Varian HyperArc as a planning and treatment solution for whole brain radiotherapy (WBRT) with hippocampal sparing following Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Ten patients previously treated for intracranial lesions were retrospectively planned for WBRT with hippocampal sparing using HyperArc and a 2-arc coplanar VMAT technique. The whole brain and hippocampus were delineated on fused MRI and CT datasets. The planning target volume (PTV), defined as the whole brain excluding the hippocampal avoidance region, was prescribed 30 Gy in 10 fractions. Plans were evaluated using dosimetric parameters which included the volume of 105% of the prescription dose (V105%) and the maximum dose to the PTV, and the minimum dose to the hippocampus. The planning time, delivery time, and delivery quality assurance (QA) results were also evaluated. Statistical significance was performed between the HyperArc and coplanar VMAT metrics using the Wilcoxon signed-rank test with a significance level of 0.05. All plans met RTOG 0933 dosimetric criteria. HyperArc plans demonstrated significant improvements in PTV dosimetric quality which included a reduced V105% of 6 ± 7% and decreased maximum dose of 1.3 ± 0.3 Gy, compared to coplanar VMAT. Significant OAR sparing was also found for HyperArc plans that included a decreased minimum dose to the hippocampus of 0.3 ± 0.3 Gy. Coplanar VMAT plans resulted in significantly shorter planning and delivery times, compared to HyperArc, by 2.4 minutes and 1.5 minutes, respectively. No significant difference was found between the delivery QA results. This study demonstrated using Varian HyperArc as a planning and treatment solution for WBRT with hippocampal sparing following RTOG 0933 dosimetric criteria. The primary advantages of WBRT with hippocampal sparing using HyperArc, compared to coplanar VMAT, are the gains in OAR sparing and reduced high dose volumes to the PTV.

Intrafraction motion during frameless radiosurgery using Varian HyperArcTM and BrainLab ElementsTM immobilization systems.

Commercial systems such as Varian HyperArcTM and BrainLab Elements MultiMetTM have been developed that allow radiosurgery treatment of multiple brain metastases using a single isocenter. Each software package places increased demands on frameless immobilization and requires the use of a specific immobilization system: the QFix-Encompass system for Varian and the BrainLab frameless-mask system for BrainLab. At our institution, patients receiving traditional radiosurgery (one isocenter per target lesion) were treated using both immobilization systems. Intrafraction motion was determined for each patient using multiple cone-beam CT scans and the same image-registration software during treatment. There were no statistically-significant differences in mean absolute translational shifts between the two mask systems, with a mean 3D-vector motion of approximately 0.43 mm for both systems. There were also no statistically-significant differences in the mean absolute rotational shifts between the two mask systems. Although the average residual errors were insignificant between the mask systems, special attention should be paid to individual maximum shifts with both systems. Large maximum rotational misalignments could present significant misalignment of lesions as distance increases from the isocenter. Finally, large maximum shifts highlight the need for real-time monitoring of patient movement during radiosurgery of multiple lesions using a single isocenter.

Effect of Surgeon Factors on Long-Term Patient-Reported Outcomes After Breast-Conserving Therapy in Older Breast Cancer Survivors.

BACKGROUND: The effect of surgeon factors on patient-reported quality-of-life outcomes after breast-conserving therapy (BCT) is unknown and may help patients make informed care decisions. METHODS: We performed a survey study of women aged ≥ 67 years with non-metastatic breast cancer diagnosed in 2009 and treated with guideline-concordant BCT, to determine the association of surgeon factors with patient-reported outcomes. The treating surgeon was identified using Medicare claims, and surgeon factors were identified via the American Medical Association Physician Masterfile. The primary outcome was patient-reported cosmetic satisfaction measured by the Cancer Surveillance and Outcomes Research Team (CanSORT) Satisfaction with Breast Cosmetic Outcome instrument, while secondary outcomes included BREAST-Q subdomains. All patient, treatment, and surgeon covariables were included in a saturated multivariable linear regression model with backward elimination applied until remaining variables were p < 0.1. RESULTS: Of 1650 women randomly selected to receive the questionnaire, 489 responded, of whom 289 underwent BCT. Median age at diagnosis was 72 years and the time from diagnosis to survey was 6 years. The mean adjusted CanSORT score was higher for patients treated by surgical oncologists than patients treated by non-surgical oncologists (4.01 [95% confidence interval [CI] 3.65-4.38] vs. 3.53 [95% CI 3.28-3.77], p = 0.006). Similarly, mean adjusted BREAST-Q Physical Well-Being (91.97 [95% CI 86.13-97.80] vs. 83.04 [95% CI 80.85-85.22], p = 0.006) and Adverse Radiation Effects (95.28 [95% CI 91.25-99.31] vs. 88.90 [95% CI 86.23-91.57], p = 0.004) scores were better among patients treated by surgical oncologists. CONCLUSIONS: Specialized surgical oncology training is associated with improved long-term patient-reported outcomes. These findings underscore the value of specialized training and may be useful to patients choosing their care team.

Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer.

OBJECTIVE: To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer. METHODS: We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT + RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT ±â€¯CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001). CONCLUSIONS: Combined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.

Long-term decision regret surrounding systemic therapy in older breast cancer survivors: A population-based survey study.

INTRODUCTION: Little is known regarding regret experienced by older breast cancer survivors surrounding the choice for adjuvant systemic therapy, which limits providers' ability to optimally engage in the shared decision-making process. To address this, we evaluated endocrine therapy and chemotherapy decisional regret in a population-based cohort of older breast cancer survivors. MATERIALS AND METHODS: Nationally comprehensive Medicare claims identified women age ≥67 living in the US with non-metastatic breast cancer diagnosed in 2009 and still alive in 2015. The Decision Regret Scale, a validated index that assesses regret regarding treatment decisions on a scale of 0 (no regret) to 100, was used to measure regret for endocrine therapy and chemotherapy approximately 6 years after diagnosis and was adjusted for sampling weight. Multivariable logistic regression adjusted for patient, demographic, and treatment characteristics identified predictors of endocrine therapy and chemotherapy decision regret. RESULTS: Of the 480 respondents, 299 patients (61.1%) reported receiving endocrine therapy and 133 (27%) chemotherapy. The overall weighted decision-regret score was 17.2 (95%CI 13.6-20.8) for endocrine therapy and 17.7 (95%CI 12.1-23.3) for chemotherapy. Risk factors for higher endocrine therapy regret included white race (referent non-white race; estimate 12.8, 95%CI 3.0-22.7; P = 0.01) and post-graduate educational attainment (referent college education; 11.6, 95%CI 1.9-21.3; P = 0.02). The only risk factor for chemotherapy regret, albeit marginal, was age ≥75 (referent age 67-74; 12.0, 95%CI -0.1-24.2; P = 0.05) CONCLUSION: Overall, decision regret levels regarding systemic therapy in older breast cancer survivors are reassuringly low. However, further studies are needed to explore drivers of regret in certain vulnerable subgroups of patients.

Local Therapy Decisional Regret in Older Women With Breast Cancer: A Population-Based Study.

PURPOSE: Older women with nonmetastatic breast cancer can often choose from several surgery and radiation treatment options. Little is known regarding how these choices contribute to decisional regret, which is a negative emotion reflecting the idea that another surgery or radiation decision might have been preferable. We sought to characterize the burden of and examine potential risk factors for local therapy decisional regret among a population-based cohort of older breast cancer survivors. METHODS AND MATERIALS: National Medicare claims for age ≥67 female breast cancer incident in 2009 identified patients treated with lumpectomy plus whole-breast irradiation, brachytherapy, or endocrine therapy or mastectomy with or without radiation. We sampled 330 patients per treatment group (N = 1650), of whom 1253 agreed to receive a paper survey including the Decisional Regret Scale and EQ-5D-3L Health-Utility Scale. Local therapy regret was defined as neutral or worse response to questions regarding surgery- or radiation-related decisional regret. Local therapy regret risk factors were evaluated using a multivariable generalized linear model. Association of local therapy regret with health utility was modeled using multivariable linear regression. RESULTS: The response rate was 30.2% (n = 498 of 1650); 421 surveys were included in this analysis. Median diagnosis age was 72 years, and surveys were completed 6 years after diagnosis. Overall, 23.8% of respondents (n = 100) reported experiencing local therapy decisional regret. Type of local therapy was not associated with local therapy regret. Predictors of increased regret included black race (risk ratio [RR], 2.09; 95% confidence interval [CI], 1.33-3.29), high school education or less (RR, 1.87; 95% CI, 1.27-2.75), and axillary nodal dissection (RR, 2.13; 95% CI, 1.33-3.41). Local therapy regret was not associated with health utility (P = .37). CONCLUSIONS: Local therapy regret afflicts nearly one quarter of our cohort of older breast cancer survivors, and it is associated with black race, less education, and more extensive nodal dissection, but not breast surgery. Regret is distinct from health utility, suggesting that it is a unique psychosocial construct that merits further study and mitigation strategies.

Long-term Patient-Reported Outcomes in Older Breast Cancer Survivors: A Population-Based Survey Study.

PURPOSE: For older women with breast cancer, local therapy options may include lumpectomy plus whole-breast irradiation (Lump + WBI), lumpectomy plus brachytherapy (Lump + Brachy), lumpectomy alone (Lump alone), mastectomy without radiation therapy (Mast alone), and mastectomy plus radiation therapy (Mast + RT). We surveyed a population-based cohort of older breast cancer survivors to assess the association of local therapy with long-term quality-of-life outcomes. METHODS AND MATERIALS: We used nationally comprehensive Medicare claims to identify women aged ≥67 years in whom nonmetastatic breast cancer was diagnosed in 2009, who were treated with 1 of the 5 aforementioned treatment options, and who were still alive in 2015. From this cohort, 1650 patients (330 patients per treatment) were randomly selected. A survey that included the CanSORT (Cancer Surveillance and Outcomes Research Team) Satisfaction with Breast Cosmetic Outcome, BREAST-Q, Decisional Regret Scale, and EQ-5D-3L was mailed to potential participants. We used multivariable linear regression to assess associations between local therapy and outcomes after adjusting for patient, disease, and treatment covariates. RESULTS: Among the 489 women who returned the surveys (30% response rate), the median age at diagnosis was 72 years (range, 67-87 years). The interval from diagnosis to survey completion was approximately 6 years for all patients. Compared with Lump + WBI (adjusted score, 3.40), the CanSORT cosmetic satisfaction scores were higher for Lump + Brachy (score, 3.77; P = .007) and Lump alone (score, 3.80; P = .04) and lower for Mast + RT (score, 3.01; P = .006). Similar trends were seen for BREAST-Q cosmetic satisfaction. BREAST-Q psychosocial, sexual, and physical well-being and EQ-5D-3L global health status tended to be better in patients treated with less irradiation and less surgery. BREAST-Q adverse radiation effects were worse for Lump + WBI compared with Lump + Brachy. Decisional regret regarding surgery and radiation therapy did not differ across groups. Compared with patients treated with Lump + WBI, patients treated with Lump + Brachy and Lump alone reported slightly higher rates of in-breast recurrence (excess risk of 5.8% and 6.4%, respectively; P = .01). CONCLUSIONS: In this nationally diverse cohort, less irradiation and less surgery were associated with better long-term quality-of-life outcomes. However, patient regret regarding surgery and radiation therapy was similar across all groups.

Patterns and correlates of treatment failure in relation to isodose distribution in non-small cell lung cancer: An analysis of 1522 patients in the modern era.

BACKGROUND AND PURPOSE: To examine the relationship between radiation dose and tumor control in limited stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We searched a database of 1552 patients who received radiation therapy for non-metastatic NSCLC between 2000 and 2016. The primary endpoint was freedom from in-field failure. RESULTS: Increasing BED correlated with decreasing estimated gross tumor volume-planning target volume expansion, and on multivariable analysis increasing BED was associated with an increased chance of field-edge failures (hazard ratio [HR] 1.032, 95% confidence interval [CI] 1.004-1.062, P = 0.027). Increasing BED also correlated with improved freedom from in-field failure on multivariable analysis (HR 0.978, 95% CI 0.964-0.993, P = 0.003), with the dose-response curve showing a sigmoidal relationship between increasing BED and freedom from in-field failure. CONCLUSION: In this large study of patients treated in the modern era with varying dose fractionation regimens, higher BED was associated with improved freedom from in-field failure, and that this relationship appeared to be consistent with the classically described sigmoid shape. We also found that increased BED was associated with higher field-edge failures, implying that margin size may need to be further studied in patients receiving ablative regimens of radiation.

Challenges to delivery and effectiveness of adjuvant radiation therapy in elderly patients with node-positive vulvar cancer.

OBJECTIVE: To examine adjuvant radiation therapy (RT) use, patterns of RT delivery, and clinical outcomes in older patients with node-positive vulvar cancer. METHODS: Using SEER-Medicare linked data, we identified 444 patients (age≥66years) with node-positive squamous cell vulvar carcinoma, without distant metastases, and treated with primary surgery between 1991 and 2009. We used claims to examine RT use and the following delivery metrics: 1) completion of ≥20 fractions, 2) treatment duration <8weeks, 3) <1week of intra-treatment break, and 4) treatment interval from surgery to start of RT <8weeks. We tested associations between RT use and metrics with overall (OS) and cause-specific survival (CSS) using multivariate proportional hazards regression. RESULTS: Median age was 78years (interquartile range [IQR]=74-83). Median follow-up was 17months (IQR=9-40). Three hundred six patients (69%) received RT. Three delivery metrics were associated with improved outcomes: completion of ≥20 fractions, treatment duration <8weeks, and <1week of intra-treatment break. Patients who achieved these 3 metrics demonstrated better disease outcomes compared with surgery alone (OS hazard ratio [HR] for death=0.62, 95% confidence interval [CI]=0.46-0.82, P=0.001; CSS HR=0.58, 95% CI=0.40-0.85,P=0.005). Patients not achieving RT metrics demonstrated marginal improvements in disease outcomes over surgery alone (OS HR=0.73, 95% CI=0.55-0.99,P=0.04; CSS HR=0.76, 95% CI=0.52-1.11, P=0.16). Notably, only 51% of patients who received RT achieved all benchmarks. CONCLUSIONS: In this cohort of older women with node-positive vulvar cancer, achieving metrics for RT delivery was an important factor for optimizing disease benefits from treatment.

Outcomes and toxicity following high-dose radiation therapy in 15 fractions for non-small cell lung cancer.

PURPOSE: Accelerated hypofractionated radiation therapy (AHRT) is increasingly used for select lung cancer patients. We evaluated clinical outcomes and predictors of pulmonary/esophageal toxicity in patients treated with ≥52.5 Gy in 15 fractions. METHODS AND MATERIALS: We evaluated 229 patients treated with radiation therapy doses ≥52.5 Gy in 15 fractions for non-small cell lung cancer from January 2009 through January 2016. Toxicity was scored using Common Terminology Criteria for Adverse Events, v4.0. Univariate and multivariate logistic regression was used to identify predictors of toxicity. Overall survival, progression-free survival, and local control were estimated using the Kaplan-Meier method. Predictors of clinical outcome were modeled using Cox proportional hazards regression. RESULTS: Median follow-up was 7 months. Forty-two patients (19%) developed grade ≥2 pneumonitis, and 9 (4%) developed grade ≥3 esophagitis. In multivariate analysis, age >75 years (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.24-5.25; P = .01) and percentage of lung volume receiving doses of >10 Gy higher than 32% were associated with grade ≥2 pneumonitis (OR, 2.79; 95% CI, 1.39-5.79; P = .005). On univariate analysis, esophagus mean dose ≥17 Gy (OR, 10.14; 95% CI, 1.82-189.8; P = .006), gross tumor volume size ≥71 cm3 (P = .002), and planning target volume size ≥409 cm3 (P = .02) were associated with development of grade ≥3 esophagitis. In patients with stage II/III disease (n = 73), median local control was not reached, median overall survival was 14 months, and median progression-free survival was 6 months. CONCLUSIONS: AHRT in 15 fractions can be safe and effective. Consideration for using AHRT with immunotherapy and sequential chemotherapy for improved out-of-radiation field and distant control is warranted.

Incidence and predictors of chest wall toxicity after high-dose radiation therapy in 15 fractions.

PURPOSE: Fifteen fraction treatment schedules are increasingly used to deliver high doses of radiation therapy (RT) to both lung and hepatobiliary malignancies. The purpose of our study was to examine the incidence and predictors of chest wall (CW) toxicity in patients treated with this regimen. METHODS AND MATERIALS: We evaluated 135 patients treated with RT to doses ≥52.5 Gy in 15 fractions for thoracic and hepatobiliary malignancies between January 2009 and December 2012. We documented patient characteristics and CW dosimetric parameters for each case. Toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0, criteria for radiation dermatitis and CW pain. Patient characteristics and CW dosimetric parameters were evaluated for their association with CW toxicity using proportional hazards regression. RESULTS: Median follow-up was 9 months from the start of RT. Forty-eight patients (36%) developed dermatitis at a median time of 18 days. In multivariable analysis, the absolute volume of CW (in cm3) receiving 40 Gy (V40) ≥120 cm3 was associated with the occurrence of dermatitis (hazard ratio, 3.12; 95% confidence interval, 1.74-5.60; P < .001). Twenty-one patients (16%) developed CW pain (20 grade 1, 1 grade 2) at a median time of 3 months. In multivariable analysis, CW V40 ≥150 cm3 was associated with the occurrence of CW pain (hazard ratio, 2.65; 95% confidence interval, 1.12-6.24; P = .03). The absolute rate of CW pain in patients with V40 <150 cm3 was 11% versus 26% in patients with V40 ≥150 cm3 (P = .03). CONCLUSIONS: Hypofractionated RT with 15 fraction regimens results in an acceptable incidence of CW toxicity, specifically CW pain. We recommend a dose constraint of V40 <150 cm3 to minimize this adverse event.

Comparison of Computed Tomography- and Magnetic Resonance Imaging-based Clinical Target Volume Contours at Brachytherapy for Cervical Cancer.

PURPOSE: We prospectively compared computed tomography (CT)- and magnetic resonance imaging (MRI)-based high-risk clinical target volume (HR-CTV) contours at the time of brachytherapy for cervical cancer in an effort to identify patients who might benefit most from MRI-based planning. METHODS AND MATERIALS: Thirty-seven patients who had undergone a pretreatment diagnostic MRI scan were included in the analysis. We delineated the HR-CTV on the brachytherapy CT and brachytherapy MRI scans independently for each patient. We then calculated the absolute volumes for each HR-CTV and the Dice coefficient of similarity (DC, a measure of spatial agreement) for the HR-CTV contours. We identified the clinical and tumor factors associated with (1) a discrepancy in volume between the CT HR-CTV and MRI HR-CTV contours; and (2) DC. The mean values were compared using 1-way analysis of variance or paired or unpaired t tests, as appropriate. Simple and multivariable linear regression analyses were used to model the effects of covariates on the outcomes. RESULTS: Patients with International Federation of Gynecology and Obstetrics stage IB to IVA cervical cancer were treated with intracavitary brachytherapy using tandem and ovoid (n=33) or tandem and cylinder (n=4) applicators. The mean CT HR-CTV volume (44.1 cm3) was larger than the mean MRI HR-CTV volume (35.1 cm3; P<.0001, paired t test). On multivariable analysis, a higher body mass index (BMI) and tumor size ≥5 cm with parametrial invasion on the MRI scan at diagnosis were associated with an increased discrepancy in volume between the HR-CTV contours (P<.02 for both). In addition, the spatial agreement (as measured by DC) between the HR-CTV contours decreased with an increasing BMI (P=.013). CONCLUSIONS: We recommend MRI-based brachytherapy planning for patients with tumors >5 cm and parametrial invasion on MRI at diagnosis and for those with a high BMI.

Longitudinal analysis of patient-reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole-breast irradiation.

BACKGROUND: The authors compared longitudinal patient-reported outcomes and physician-rated cosmesis with conventionally fractionated whole-breast irradiation (CF-WBI) versus hypofractionated whole-breast irradiation (HF-WBI) within the context of a randomized trial. METHODS: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes. RESULTS: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time). CONCLUSIONS: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society.

Indications for adjuvant radiation therapy in breast cancer: a review of the evidence and recommendations for clinical practice.

Radiation therapy (RT) plays an important role in the curative management of all stages of breast cancer. The optimal application of adjuvant RT is an area of continuous investigation, and the indications for treatment are refined with each new trial. This article reviews the evidence for adjuvant RT across five distinct clinical scenarios, with additional discussion of RT targets, techniques, and doses where appropriate.

Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis.

PURPOSE: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. PATIENTS AND METHODS: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). RESULTS: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. CONCLUSION: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.