Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

The dosimetric benefit of in-advance respiratory training for deep inspiration breath holding is realized during daily treatment in left breast radiotherapy: A comparative retrospective study of serial surface motion tracking.

INTRODUCTION: A novel approach of in-advance preparatory respiratory training and practice for deep inspiration breath holding (DIBH) has been shown to further reduce cardiac dose in breast cancer radiotherapy patients, enabled by deeper (extended) DIBH. Here we investigated the consistency and stability of such training-induced extended DIBH after training completion and throughout the daily radiotherapy course. METHODS: Daily chestwall motion from real-time surface tracking transponder data was analysed in 67 left breast radiotherapy patients treated in DIBH. Twenty-seven received preparatory DIBH training/practice (prep Trn) 1-2 weeks prior to CT simulation, resulting in an extended DIBH (ext DIBH) and reduced cardiac dose at simulation. Forty had only conventional immediate pre-procedure DIBH instruction without prep Trn and without extended DIBH (non-Trn group). Day-to-day variability in chestwall excursion pattern during radiotherapy was compared among the groups. RESULTS: The average of daily maximum chestwall excursions was overall similar, 2.5 ± 0.6 mm for prep Trn/ext DIBH vs. 2.9 ± 0.8 mm for non-Trn patients (P = 0.24). Chestwall excursions beyond the 3-mm tolerance threshold were less common in the prep Trn/ext DIBH group (18.8% vs. 37.5% of all fractions within the respective groups, P = 0.038). Among patients with cardiopulmonary disease those with prep Trn/ext DIBH had fewer chestwall excursions beyond 3 mm (9.4% vs. 46.7%, P = 0.023) and smaller average maximum excursions than non-Trn patients (2.4 ± 0.3 vs. 3.0 ± 0.6 mm, P = 0.047, respectively). CONCLUSION: Similar stability of daily DIBH among patients with and without preparatory training/practice suggests that the training-induced extended DIBH and cardiac dose reductions were effectively sustained throughout the radiotherapy course. Training further reduced beyond-tolerance chestwall excursions, particularly in patients with cardiopulmonary disease.

COVID-19 impact on timing of brachytherapy treatment and strategies for risk mitigation.

PURPOSE: The purpose of this study was to highlight the importance of timely brachytherapy treatment for patients with gynecologic, breast, and prostate malignancies, and provide a framework for brachytherapy clinical practice and management in response to the COVID-19 pandemic. METHODS AND MATERIALS: We review amassing evidence to help guide the management and timing of brachytherapy for gynecologic, breast, and prostate cancers. Where concrete data could not be found, peer-reviewed expert opinion is provided. RESULTS: There may be a significant negative impact on oncologic outcomes for patients with gynecologic malignancies who have a delay in the timely completion of therapy. Delay of prostate or breast cancer treatment may also impact oncologic outcomes. If a treatment delay is expected, endocrine therapy may be an appropriate temporizing measure before delivery of radiation therapy. The use of shorter brachytherapy fractionation schedules will help minimize patient exposure and conserve resources. CONCLUSIONS: Brachytherapy remains a critical treatment for patients and may shorten treatment time and exposure for some. Reduced patient exposure and resource utilization is important during COVID-19. Every effort should be made to ensure timely brachytherapy delivery for patients with gynecologic malignancies, and endocrine therapy may help temporize treatment delays for breast and prostate cancer patients. Physicians should continue to follow developing institutional, state, and federal guidelines/recommendations as challenges in delivering care during COVID-19 will continue to evolve.

Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol.

INTRODUCTION: A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer. METHODS: We are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events. ETHICS AND DISSEMINATION: The RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets. TRIAL REGISTRATION NUMBER: NCT02603341.

Predictors of cardiac and lung dose sparing in DIBH for left breast treatment.

This retrospective study of left breast radiation therapy (RT) investigates the correlation between anatomical parameters and dose to heart or/and left lung in deep inspiration breath-hold (DIBH) compared to free-breathing (FB) technique. Anatomical parameters of sixty-seven patients, treated with a step-and-shoot technique to 50 Gy or 50.4 Gy were included. They consisted of the cardiac contact distances in axial (CCDax) and parasagittal (CCDps) planes, and the lateral heart-to-chest distance (HCD). Correlation analysis was performed to identify predictors for heart and lung dose sparing. Paired t-test and linear regression were used for data analysis with significance level of p = 0.05. All dose metrics for heart and lung were significantly reduced with DIBH, however 21% of patients analyzed had less than 1.0 Gy mean heart dose reduction. Both FB-CCDpsdistance and FB-HCD correlated with FB mean heart dose and mean DIBH heart dose reduction. The strongest correlation was observed for the ratio of FB-CCDpsand FB-HCD with heart dose sparing. A FB-CCDps and FB-HCD model was developed to predict DIBH induced mean heart dose reduction, with 1.04 Gy per unit of FB-CCDps/FB-HCD. Variation between predicted and actual mean heart dose reduction ranged from -0.6 Gy to 0.6 Gy. In this study, FB-CCDps and FB-HCD distance served as predictors for heart dose reduction with DIBH equally, with FB-CCDps/FB-HCD as a stronger predictor. These parameters and the prediction model could be further investigated for use as a tool to better select patients who will benefit from DIBH.

Accuracy and stability of deep inspiration breath hold in gated breast radiotherapy - A comparison of two tracking and guidance systems.

PURPOSE: To characterize reproducibility of patient breath-hold positioning and compare tracking system performance for Deep Inspiration Breath Hold (DIBH) gated left breast radiotherapy. METHODS: 29 consecutive left breast DIBH patients (655 fractions) were treated under the guidance of Calypso surface beacons with audio-feedback and 35 consecutive patients (631 fractions) were treated using C-RAD Catalyst HD surface imaging with audiovisual feedback. The Calypso system tracks a centroid determined by two radio-frequency transponders, with a manually enforced institutional tolerance, while the surface image based CatalystHD system utilizes real-time biometric feedback to track a pre-selected point with an institutional tolerance enforced by the Elekta Response gating interface. DIBH motion data from Calypso was extracted to obtain the displacement of breath hold marker in ant/post direction from a set-zero reference point. Ant/post point displacement data from CatalystHD was interpreted by computing the difference between raw tracking points and the center of individual gating windows. Mean overall errors were compared using Welsh's unequal variance t-test. Wilcoxon rank sum test were used for statistical analysis with P < 0.05 considered significant. RESULTS: Mean overall error for Calypso and CatalystHD were 0.33 ±â€¯1.17 mm and 0.22 ±â€¯0.43 mm, respectively, with t-test comparison P-value < 0.034. Absolute errors for Calypso and CatalystHD were 0.95 ±â€¯0.75 mm and 0.38 ±â€¯0.30 mm, respectively, with Wilcoxon rank sum test P-value <2×10-16. Average standard deviation per fraction was found to be 0.74 ±â€¯0.44 mm for Calypso patients versus 0.54 ±â€¯0.22 mm for CatalystHD. CONCLUSION: Reduced error distribution widths in overall positioning, deviation of position, and per fraction deviation suggest that the use of functionalities available in CatalystHD such as audiovisual biofeedback and patient surface matching improves accuracy and stability during DIBH gated left breast radiotherapy.

Cardiac sparing characteristics of internal mammary chain radiotherapy using deep inspiration breath hold for left-sided breast cancer.

BACKGROUND: While breast radiotherapy typically includes regional nodal basins, the treatment of the internal mammary nodes (IMN) has been controversial due to concern for long-term cardiac toxicity. For high risk patients where IMN treatment is warranted, there is limited data with regards to the degree of heart sparing conferred by modern techniques. In this study, we sought to analyze the specific heart sparing metrics conferred by deep inspiration breath hold (DIBH) in the setting of IMN irradiation. METHODS: From 2012 to 2015, 168 consecutive patients were treated with adjuvant left-sided radiotherapy using DIBH. Retrospective review identified 49 patients who received nodal irradiation, either to a supraclavicular field (SCF) and IMN (16), or to the SCF alone (33). Cardiac mean dose and dose volumes were calculated from free breathing (FB) and DIBH treatment plans, and compared by Wilcoxon signed-rank and Mann-Whitney U tests. RESULTS: DIBH achieved significant reductions in mean heart dose (p < 0.001) in both the IMN treated group from 6.73 Gy to 2.79 Gy (- 56.4%) and the IMN untreated group from 4.77 Gy to 1.55 Gy (- 63.7%). There was a 7.3% difference in relative reduction that was not statistically significant (p = 0.216). Relative reductions in heart dose volume measures were all significantly lower for IMN-irradiated patients (p ≤ 0.012), with the greatest deficits at V5 that gradually diminish with increasing dose (V25). CONCLUSIONS: The relative heart sparing benefits of the DIBH technique are retained even with IMN inclusion. However, the addition of IMN irradiation is associated with an intrinsically greater heart dose, which translates to an estimated 9.2% proportional increase in the risk of a subsequent major coronary event. In the setting of effective cardiac sparing techniques, clinicians should take these considerations into account to guide when IMN treatment is warranted.

High-risk prostate cancer with Gleason score 8-10 and PSA level ≤15 ng/mL treated with permanent interstitial brachytherapy.

PURPOSE: With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) ≥8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS ≥8 and a PSA level ≤15 ng/mL with or without androgen-deprivation therapy (ADT). METHODS AND MATERIALS: From April 1995 to October 2005, 174 patients with GS ≥8 and a PSA level ≤15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level ≤0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. RESULTS: Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. CONCLUSIONS: Patients with GS ≥8 and PSA level ≤15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.

Androgen deprivation therapy: a survival benefit or detriment in men with high-risk prostate cancer?

Androgen deprivation therapy (ADT) has been used in the management of prostate cancer for more than four decades. Initially, hormone therapy was given largely for palliation of symptomatic metastases. Following several randomized trials of patients with intermediate- to high-risk prostate cancer that demonstrated improvements in biochemical control and survival with the addition of ADT to external beam radiotherapy, there was a dramatic increase in the use of hormone therapy in the definitive setting. More recently, the safety of ADT has been questioned, as some studies have suggested an association of hormone therapy with increased cardiovascular morbidity and mortality. This is particularly worrisome in light of practice patterns that show ADT use extrapolated to situations for which there has been no proven benefit. In the setting of dose escalation with modern radiotherapy, in conjunction with the latest concerns about cardiovascular morbidity with ADT, the magnitude of expected benefit along with potential risks of ADT use must be carefully considered for each patient.

Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system.

BACKGROUND: The management of Merkel cell carcinoma (MCC) has been complicated by a lack of detailed prognostic data and by the presence of conflicting staging systems. OBJECTIVE: We sought to determine the prognostic significance of tumor size, clinical versus pathologic nodal evaluation, and extent of disease at presentation and thereby derive the first consensus staging/prognostic system for MCC. METHODS: A total of 5823 prospectively enrolled MCC cases from the National Cancer Data Base had follow-up data (median 64 months) and were used for prognostic analyses. RESULTS: At 5 years, overall survival was 40% and relative survival (compared with age- and sex-matched population data) was 54%. Among all MCC cases, 66% presented with local, 27% with nodal, and 7% with distant metastatic disease. For cases presenting with local disease only, smaller tumor size was associated with better survival (stage I, ≤2 cm, 66% relative survival at 5 years; stage II, >2 cm, 51%; P < .0001). Patients with clinically local-only disease and pathologically proven negative nodes had better outcome (76% at 5 years) than those who only underwent clinical nodal evaluation (59%, P < .0001). LIMITATIONS: The National Cancer Data Base does not capture disease-specific survival. Overall survival for patients with MCC was therefore used to calculate relative survival based on matched population data. CONCLUSION: Although the majority (68%) of patients with MCC in this nationwide cohort did not undergo pathologic nodal evaluation, this procedure may be indicated in many cases as it improves prognostic accuracy and has important treatment implications for those found to have microscopic nodal involvement.

Radiation monotherapy as regional treatment for lymph node-positive Merkel cell carcinoma.

BACKGROUND: : Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high risk of lymph node involvement. To the authors' knowledge, few data have been published to date regarding the optimal regional therapy for lymph node-positive patients. This cohort study was performed to analyze the outcomes of patients with lymph node-positive MCC treated with lymph node irradiation as definitive therapy compared with completion lymphadenectomy (CLND). METHODS: : Fifty patients with lymph node involvement of MCC at presentation and adequate follow-up data were included in this analysis. Forty-three of these patients were enrolled and followed prospectively. Twenty-six patients presented with microscopic lymph node disease, and 24 patients presented with palpable lymph node involvement. RESULTS: : Regional control for patients with microscopically involved lymph nodes was 100% regardless of treatment modality-definitive lymph node irradiation (n = 19) or CLND +/- radiotherapy (n = 7) with median follow-up of 18 months. Patients with clinically positive lymph nodes had 2-year regional recurrence-free survival rate of 78% and 73% in the definitive lymph node irradiation (n = 9) and CLND +/- radiotherapy (n = 15) groups, respectively (P = .8) with a median follow-up of 16 months. CONCLUSIONS: : To the best of the authors' knowledge, the current study is the largest series published to date of radiation monotherapy as regional treatment for lymph node-positive MCC. Lymph node irradiation alone to positive regional lymph nodes was found to confer an excellent regional control rate that was comparable to CLND for both microscopic and palpable lymph node disease. There was no difference noted with regard to overall survival. Given their similar efficacy, the choice between these lymph node therapies may be based on the clinical scenario and anticipated side effect profiles. Cancer 2010. (c) 2010 American Cancer Society.

Prostatic acid phosphatase adversely affects cause-specific survival in patients with intermediate to high-risk prostate cancer treated with brachytherapy.

OBJECTIVES: To perform a retrospective analysis to assess the utility of pretreatment serum prostatic acid phosphatase (PAP) as a predictor of cause-specific survival (CSS) in patients with higher risk prostate cancer treated with palladium-103 (103Pd) brachytherapy and supplemental external beam radiotherapy (EBRT). METHODS: From 1992 to 1996, 193 patients with clinically localized prostate adenocarcinoma, a pretreatment PAP level, and Gleason score 7 or more, and/or a prostate-specific antigen (PSA) level of 10 ng/mL or more were treated with 103Pd brachytherapy and supplemental EBRT. The patients underwent EBRT of 41.4 Gy to a limited pelvic field and 103Pd brachytherapy with a prescribed minimum 103Pd dose of 80 Gy. Multivariate analysis was performed to analyze the predictive value of PAP, PSA, and Gleason score on CSS. RESULTS: The 10-year CSS rate for patients with a PAP level of less than 1.5, 1.5 to 2.4, and 2.5 U/L or more was 93%, 87%, and 75%, respectively (P = 0.013). The 10-year CSS rate for patients with a PSA level of less than 10, 10 to 20, and greater than 20 ng/mL was 92%, 76%, and 83%, respectively (P = 0.393). The 10-year CSS rate for patients with a Gleason score of 6, 7, 8, and 9 was 90%, 89%, 70%, and 68%, respectively (P = 0.002). On Cox multivariate regression analysis, PAP (hazard ratio 1.31, P <0.0001) and Gleason score (hazard ratio 2.37, P = 0.0007) were associated with CSS. PSA was not predictive of CSS (P = 0.393). CONCLUSIONS: The results of this study demonstrated that PAP is a stronger predictor of CSS than PSA or Gleason score in men with higher risk prostate cancer treated with 103Pd brachytherapy and EBRT. Given the findings of this analysis, the use of PAP should be reconsidered in these patients.

Treatment of oropharyngeal squamous cell carcinoma with external beam radiation combined with interstitial brachytherapy.

BACKGROUND: We reviewed the outcomes of oropharyngeal squamous cell carcinoma treated with external beam radiation and interstitial brachytherapy. METHODS: Ninety patients with squamous cell carcinoma of the oropharynx were treated with interstitial brachytherapy at the University of Utah between 1984 and 2001. Seventy-two patients received external beam radiotherapy (EBRT) followed by brachytherapy boost, 11 had surgery followed by EBRT and brachytherapy, 4 had surgery and brachytherapy, and 3 were treated with brachytherapy alone. Median doses for EBRT and brachytherapy were 50 and 24 Gy, respectively. RESULTS: Median follow-up after brachytherapy was 48.3 months for all patients. Five-year local control, disease-free survival, and overall survival were 76%, 61%, and 55%. For T1, T2, T3, and T4, 5-year local control rates were 83%, 79%, 79%, and 64%, respectively. Severe complications occurred in 13 patients, including 2 treatment-related deaths. CONCLUSIONS: EBRT combined with interstitial brachytherapy provide good local control rates for locally advanced oropharyngeal squamous cell carcinoma.

Comparison of outcomes for patients with medically inoperable Stage I non-small-cell lung cancer treated with two-dimensional vs. three-dimensional radiotherapy.

PURPOSE: This retrospective analysis was performed to assess the outcomes of three-dimensional (3D) conformal radiotherapy and two-dimensional (2D) planning. METHODS AND MATERIALS: Between 1978 and 2003, 200 patients with Stage I non-small-cell lung cancer (NSCLC) were treated with radiotherapy alone at M.D. Anderson Cancer Center. Eighty-five patients were treated with 3D conformal radiotherapy. For the 3D group, median age, radiation dose, and follow-up was 73 (range, 50-92), 66 Gy (range, 45-90.3 Gy), and 19 months (range, 3-77 months), respectively; and for the 2D group, 69 (range, 44-88), 64 Gy (range, 20-74 Gy), 20 months (range, 1-173 months), respectively. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rates were analyzed. RESULTS: There was no statistically significant difference in patient and tumor characteristics between 2D and 3D groups, except the 3D patients were older (p = 0.006). The OS, DSS, and LRC rates were significantly higher in patients who were treated by 3D conformal radiotherapy. Two- and 5-year OS for the 3D group were 68% and 36%, respectively, and 47% and 10% in the 2D group (p = 0.001). DSS at 2 and 5 years for the 3D group were 83% and 68%, respectively, vs. 62% and 29% in the 2D group (p < 0.001). LRC rates at 2 and 5 years for patients in the 3D group were 77% and 70% and 53% and 34% in the 2D group (p < 0.001). On univariate analysis elective, nodal irradiation was associated with decreased OS, DSS, and LRC. On multivariate analysis, 3D conformal radiotherapy was associated with increased OS and DSS. Male sex, age > or =70, weight loss > or =5%, and tumor size > or =4 cm were associated with decreased OS and DSS. CONCLUSIONS: This study demonstrates that 3D conformal radiotherapy improves outcomes in patients with medically inoperable Stage I NSCLC compared with 2D treatment and is an acceptable treatment for this group of patients.