Dose to the Left Anterior Descending Artery Correlates With Cardiac Events After Irradiation for Breast Cancer.

PURPOSE: Although global heart dose has been associated with late cardiac toxic effects in patients who received radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructure dosimetry are limited. We investigated whether dose to the left anterior descending artery (LAD) correlates with adverse cardiac events. METHODS AND MATERIALS: We identified 375 consecutively treated female patients from 2012 to 2018 who received left-sided breast or chest wall irradiation (with or without regional nodal irradiation). Medical records were queried to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses (LAD Dmean, LAD Dmax, heart Dmean, and heart Dmax) were calculated and converted to 2-Gy equivalent doses (EQD2). Univariate and multivariable Cox regression analyses were performed to determine association with cardiac toxic effects. Potential dose thresholds for each of the 4 dose parameters were identified by receiver operating characteristic (ROC) curve analysis, after which Kaplan-Meier analysis was performed to compare cardiac event-free survival based on these constraints. RESULTS: Median follow-up time was 48 months. Thirty-six patients experienced a cardiac event, and 23 patients experienced a major cardiac event. On univariate and multivariable analyses, increased LAD Dmean, LAD Dmax, and heart Dmean were associated with increased risk of any cardiac event and a major cardiac event. ROC curve analysis identified a threshold LAD Dmean EQD2 of 2.8 Gy (area under the ROC curve, 0.69), above which the risk for any cardiac event was higher (P = .001). Similar results were seen when stratifying by LAD Dmax EQD2 of 6.7 Gy (P = .005) and heart Dmean EQD2 of 0.8 Gy (P = .01). CONCLUSIONS: Dose to the LAD correlated with adverse cardiac events in this cohort. Contouring and minimizing dose to the LAD should be considered for patients receiving radiation therapy for left-sided breast cancer.

Toxicity and Efficacy After Adjuvant Vaginal Brachytherapy Using 30 Gy in 6 Fractions for Stages I and II Endometrial Cancer.

PURPOSE: This study aimed to evaluate outcomes and toxicity in patients with endometrial cancer per our institutional adjuvant vaginal cuff brachytherapy (VBT) fractionation scheme. METHODS AND MATERIALS: We identified women with International Federation of Gynecology and Oncology stages I and II endometrial cancer who underwent surgical staging and adjuvant high-dose-rate VBT without external beam radiation. All patients received 30 Gy in 6 fractions to the upper one-third of the vagina, prescribed to a depth of 5 mm and delivered twice weekly. Toxicities were prospectively elicited at each follow up, and rates of recurrence and survival were retrospectively assessed. RESULTS: We identified 247 eligible patients treated between 1992 and 2018 with a median follow up of 5.8 years (range, 0.1-24.7 years). Most patients had stage I disease (52% stage IA; 37% stage IB), and 11% of patients were stage II. Deep myometrial invasion was predictive of local recurrence (P = .002). The 5-year rates of local recurrence, regional recurrence, and distant metastases were 5%, 5%, and 7%, respectively. Five-year overall and disease-free survival were 91% and 83%, respectively. The most common grade 1 toxicities were acute fatigue (11% crude rate), urinary frequency (11%), chronic (>6 months) urinary frequency (13%), urinary incontinence (13%), and vaginal stenosis (21%). There were few grade 2 toxicities (all <5%) and no grade 3 to 5 toxicities. CONCLUSIONS: The adjuvant VBT fractionation scheme of 30 Gy in 6 fractions results in low rates of toxicity, with no grade ≥3 adverse events, and local control rates comparable with those from other published series using different fractionation schemes.

Left anterior descending artery avoidance in patients receiving breast irradiation.

PURPOSE: Dose to the left anterior descending artery (LAD) may be significant in patients receiving left-sided irradiation for breast cancer. We investigated if prospective contouring and avoidance of the LAD during treatment planning were associated with lower LAD dose. METHODS AND MATERIALS: We reviewed dosimetric plans for 323 patients who received left whole breast or chest wall irradiation with or without internal mammary node (IMLN) coverage between 1/2014 and 1/2019 at a single institution. The LAD was contoured prospectively for 155 cases, and techniques were utilized to minimize LAD dose. Dose-volume-histograms from these patients were compared to those of 168 patients for whom the LAD was contoured retrospectively after treatment completion. EQD2 was calculated to account for fractionation differences. RESULTS: Compared to cases where the LAD was contoured retrospectively (n = 126), prospective LAD contouring (n = 124) was associated with lower unadjusted median max and mean LAD doses for 250 patients receiving whole-breast irradiation (WBI) without IMLN coverage: 8.5 Gy vs 5.2 Gy (p < 0.0001) and 3.6 Gy vs 2.7 Gy (p < 0.0001), respectively. EQD2 median max and mean LAD doses were also lower with prospective LAD contouring: 5.2 Gy vs 3.0 Gy (p < 0.0001) and 1.9 Gy vs 1.5 Gy (p < 0.0001), respectively. Compared to cases where the LAD was contoured retrospectively (n = 42), prospective LAD contouring (n = 31) was associated with lower max LAD doses for 73 patients with IMLN coverage: 20.4 Gy vs 14.3 Gy (p = 0.042). There was a nonsignificant reduction in median mean LAD dose: 6.2 Gy vs 6.1 Gy (p = 0.33). LAD doses were reduced while maintaining IMLN coverage (mean V90%Rx >90%). CONCLUSIONS: Prospective contouring and avoidance of the LAD were associated with lower max and mean LAD doses in patients receiving WBI and with lower max LAD doses in patients receiving IMLN treatment. Further reduction in LAD dose may require stricter optimization weighting or compromise in IMLN coverage.

Omission of Axillary Lymph Node Dissection is Associated with Inferior Survival in Breast Cancer Patients with Residual N1 Nodal Disease Following Neoadjuvant Chemotherapy.

BACKGROUND: The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease. METHODS: We analyzed NCDB patients, treated between 2006 and 2014, with cT1-3, cN1, cM0 breast cancer and residual disease in 1-3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics. RESULTS: We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3-2.2, P < 0.001 for MVA), with estimated 5-year OS of 71%, compared with 77% in the ALND group (P = 0.01). Exploratory subgroup analyses showed that SLND was comparable with ALND in patients with luminal A or B tumors with a single metastatic LN (HR 1.03, 95% CI 0.59-1.8, (P = 0.91). CONCLUSIONS: Our analysis suggests that, while an ALND may not be needed for patients with limited residual nodal burden and biologically favorable tumors, SLND should not be routinely substituted for ALND in patients with ypN1 disease following NAC until its efficacy is confirmed by prospective trials.

Combined Adjuvant Chemotherapy and Radiation Therapy Improves Disease-Free Survival for Uterine Serous Cancer.

PURPOSE: Uterine serous carcinoma (USC) is a rare but aggressive endometrial cancer histology. We reviewed outcomes for patients with USC to identify the best adjuvant treatment strategy. METHODS AND MATERIALS: We retrospectively identified 162 patients with The International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA USC treated at our institution. Baseline characteristics, treatment details, clinical outcomes, and toxicity data were recorded. RESULTS: Median follow-up was 3.4 years (0.3-26 years). A variety of adjuvant therapy strategies were employed: 14% no adjuvant therapy, 28% radiation alone, 15% chemotherapy alone, and 43% combined chemotherapy and radiation. Distant metastasis was the most common type of recurrence (37% at 5 years). For patients with stage I-IVA disease, there were no significant differences in outcomes by treatment type. For patients with stage I-II disease (70% of the cohort), disease-free survival was significantly higher after chemotherapy (alone or with radiation therapy, P = .005) and after combined chemotherapy and radiation compared with all other treatments (P = .025). Toxicity outcomes were favorable, with minimal grade 3 and no grade 4 or 5 events. CONCLUSIONS: Patients with USC experience high rates of recurrence and mortality. Distant metastasis is the most common pattern of failure for all stages. For patients with early-stage disease, combined chemotherapy and radiation improves 5-year disease-free survival compared with either single adjuvant treatment alone or no adjuvant treatment. The relatively large group of patients with USC included in this study may account for our ability to detect this improvement whereas clinical trials have failed to do so, possibly owing to the relatively small percentages of patients with USC enrolled.

Outcomes After Salvage Radiation Therapy for Recurrent Endometrial Cancer in Patients With No Prior Adjuvant Therapy: An Institutional Review.

PURPOSE: After definitive surgery, women with early-stage, low-risk endometrial cancer are observed. However, some will require salvage radiation therapy for recurrence. The purpose of this study was to evaluate our experience using salvage radiation for recurrent endometrial cancer in patients who did not receive upfront adjuvant therapy. METHODS AND MATERIALS: Twenty-eight women with endometrial cancer who had undergone initial definitive hysterectomy without adjuvant therapy developed isolated local or regional recurrence and were treated with salvage radiation in our department from 2004 to 2018. Salvage radiation included whole pelvic radiation, vaginal brachytherapy, or both. Patient and tumor characteristics, treatment details, and toxicities were recorded and analyzed. RESULTS: The median time to first recurrence was 1.7 years. First recurrences consisted of local recurrence in 23 patients, regional recurrence in 4, and both in 1. The median times from hysterectomy to first recurrence, local and regional, were 1.2 and 4.0 years, respectively. All patients underwent salvage radiation for management of their first recurrence. The median total equivalent dose in 2 Gy fractions for this treatment was 67.6 Gy (37.5-81.8 Gy). Two second recurrences occurred following salvage treatment, both local recurrence, at 6.5 and 13.5 months after radiation. The 2-year rates of local control, disease-free survival, and overall survival were 93%, 80%, and 88%, respectively. Treatment was well-tolerated, with low rates of gastrointestinal and genitourinary toxicity. CONCLUSIONS: In this group of patients, salvage radiation therapy for local or regional recurrence of endometrial cancer resulted in excellent control with low rates of acute and chronic toxicities.

Sequencing of Adjuvant Chemoradiation for Advanced Stage Endometrial Cancer: Outcomes and Toxicity Profiles.

OBJECTIVES: Radiation is frequently added to chemotherapy for adjuvant treatment of advanced stage endometrial cancer. Multiple adjuvant therapy sequencing options exist, and little data is available to compare these. We compared outcomes and toxicities after "sandwich" chemoradiation (chemotherapy, then radiation, then chemotherapy) and nonsandwich sequences (chemotherapy then radiation, radiation then chemotherapy, or concurrent chemoradiation). MATERIALS AND METHODS: We recorded baseline characteristics, adjuvant treatment details, clinical outcomes, and toxicities for stage III to IVA patients who underwent surgical staging followed by both adjuvant chemotherapy and radiation therapy at our institution. Effects of adjuvant treatment order (sandwich or nonsandwich) on these outcomes were analyzed. Toxicities were graded according to CTCAE v4.0. RESULTS: We identified 107 patients with a median follow-up of 3.2 years. Five-year local, regional, and distant recurrence were 7%, 15%, and 33%; disease-free and overall survival were 61% and 68%, respectively. Outcomes did not differ by sequence group. The overall rate of acute toxicity did not differ by sequence group. The overall rate of chronic toxicity was significantly lower for sandwich patients (P<0.001), as were overall rates of chronic genitourinary (P=0.048) and gynecologic (P<0.001) toxicities. There were no grade 4 or 5 acute or chronic toxicities. CONCLUSIONS: Advanced stage endometrial cancer is an aggressive disease and adjuvant chemotherapy and radiation therapy are indicated. Clinical outcomes were similar amongst the different sequences; however, sandwich therapy led to less chronic toxicity, offering an opportunity for improved quality of life in survivorship.

Post-mastectomy radiotherapy is associated with improved overall survival in T3N0 patients who do not receive chemotherapy.

BACKGROUND AND PURPOSE: There is limited retrospective evidence addressing the utility of post-mastectomy radiotherapy (PMRT) in patients with T3N0 breast cancer. We performed a retrospective analysis of the National Cancer Database (NCDB) comparing overall survival (OS) in T3N0 patients treated with mastectomy alone (MTX) or with PMRT. MATERIALS AND METHODS: We performed a matched-cohort analysis of NCDB breast cancer patients with pT3N0 disease who did not receive NAC, or cT3N0 patients who received NAC treated between 2006 and 2014. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights. RESULTS: We identified 13,901 eligible patients. In the pT3N0 cohort, median follow-up was 47 months for the MTX group and 50 months for the PMRT group. In the cT3N0 cohort, median follow-up was 44 months for the MTX group and 46 months for the PMRT group. OS was higher in pT3N0 patients treated with PMRT compared to MTX: 7-year OS of 74% vs. 65% (P < 0.001). Doubly robust multivariable analysis showed an association between PMRT and improved OS (HR 0.78, 95% CI 0.68-0.89, P < 0.001). There was no benefit to PMRT in patients who received adjuvant chemotherapy (AC). In the NAC cohort, PMRT did not change OS, with 7-year OS of 78% with MTX and 79% with PMRT. There was a trend of improved OS with PMRT in patients with residual disease in the breast and lymph nodes (HR 0.70, 95% CI 0.46-1.07). CONCLUSION: PMRT improves OS in patients with pT3N0 disease, but the benefit appears limited to those who do not receive AC. PMRT does not improve OS in patients with cT3N0 disease who receive NAC, but there might be a benefit in patients with a poor response to chemotherapy. However, longer follow-up may be needed to make a definitive conclusion about the benefit of PMRT in patients who receive chemotherapy.

Mapping of Metastatic Level I Axillary Lymph Nodes in Patients with Newly Diagnosed Breast Cancer.

PURPOSE: We examined the distribution of pretreatment nodal metastases to the level I axilla (Ax-L1) to assess the appropriateness of current breast atlases and provide guidelines in relationship to easily identifiable anatomic landmarks for accurate delineation of this lymph node (LN) basin. METHODS AND MATERIALS: Patients with newly diagnosed breast cancer and biopsy-proven metastatic Ax-L1 LNs were identified. We related the location of each LN to its most adjacent rib and its distance from the bottom of the humeral head, axillary vessels, and a line connecting the anterior aspects of the pectoralis and latissimus dorsi muscles (P-L line). LNs were mapped onto a representative planning computed tomography scan, and their distribution was used to validate the current Radiation Therapy Oncology Group, European Society for Radiotherapy and Oncology, and Radiotherapy Comparative Effectiveness breast atlases. Furthermore, we examined metastases to a subregion encompassing the superolateral Ax-L1, irradiation of which correlates highly with lymphedema. RESULTS: We identified 106 eligible patients with 107 biopsied LNs. All LNs fell between the second and fifth ribs (mean, 3.8 ± 0.56). Mean distance from the inferior aspect of the humeral head was 4.3 ± 1.6 cm (range, 0.3-8.4). Mean distance from the inferior aspect of the axillary vessels was 2.9 ± 1.5 cm (range, -0.6 to 5.4). Mean distance from the P-L line was 0.01 ± 1.9 cm (range, -2.2 to 2.4); negative and positive values denote medial or lateral to the P-L line. A Radiation Therapy Oncology Group-compliant Ax-L1 consensus contour, created from contours by 4 attending breast radiation oncologists, partially or fully missed 45% of mapped LNs. European Society for Radiotherapy and Oncology- and Radiotherapy Comparative Effectiveness-compliant Ax-L1 similarly missed 46% and 34% of mapped LNs, respectively. LNs were most frequently missed in the lateral direction. The superolateral Ax-L1 encompassed 9.3% of the mapped LNs. CONCLUSIONS: A significant percentage of at-risk Ax-L1 tissue falls outside current contouring atlases. We propose expansion of the recommended Ax-L1 borders, most notably in the lateral direction.

Breast conserving therapy is associated with improved overall survival compared to mastectomy in early-stage, lymph node-negative breast cancer.

BACKGROUND AND PURPOSE: Recent retrospective studies suggest improved overall survival (OS) with breast conserving therapy (BCT), including breast conserving surgery and adjuvant whole breast radiotherapy, compared to mastectomy in the modern era. The patient subset most likely to benefit from BCT remains unclear, and the role of Oncotype DX Recurrence Score (RS) in this context is unknown. We compared BCT to mastectomy in early-stage, node-negative breast cancer. We further explored outcomes after stratification by RS and age. MATERIALS AND METHODS: We performed a matched-cohort analysis of National Cancer Database (NCDB) patients with pT1-2, pN0, cM0 breast cancer treated between 2006 and 2014 with BCT or mastectomy. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights. RESULTS: We identified 144,263 eligible patients treated with BCT and 87,379 patients treated with mastectomy. After IPTW-matching, OS was higher with BCT compared to mastectomy: 5-year OS of 94.4% vs. 91.8% (P < 0.001) and 7-year OS of 90% vs. 85.2% (P < 0.001). Doubly robust multivariable analysis showed an association between BCT and improved OS (HR 0.66, 95% CI, 0.64-0.69, P < 0.001). In a subset analysis, BCT was associated with improved OS in patients with RS >25, but not patients with RS ≤25. When stratified by age, only patients >50 years had improved OS with BCT. CONCLUSION: BCT is associated with improved OS compared to mastectomy in women with early-stage, node-negative breast cancer. The improvement in OS with BCT appears to be most pronounced in patients with high RS and >50 years of age. Prospective validation of these findings is required.

The Cost-Effectiveness and Value Proposition of Brachytherapy.

Brachytherapy is an effective treatment modality for a wide range of malignancies. However, brachytherapy utilization for both prostate and gynecologic malignancies has significantly declined over the last 20 years in favor of external beam radiation techniques. The cause of this decline is multifactorial, with logistical challenges, lower reimbursement, and inadequate training contributing to the preference of many radiation oncologists to more frequently recommend external beam radiation therapy. While the authors recognize the application of brachytherapy to a wider range of disease presentations among which include breast, skin, head and neck, and connective tissue cancers, in this review, we will review the analyses supporting brachytherapy as a cost-effective component of the management in patients with prostate, cervix, and endometrial cancer.

Histopathological Findings After Reirradiation Compared to First Irradiation of Spinal Bone Metastases With Stereotactic Body Radiotherapy: A Cohort Study.

BACKGROUND: Stereotactic body radiotherapy (SBRT) of the spine provides superior tumor control, but vertebral compression fractures are increased and the pathophysiological process underneath is not well understood. Data on histopathological changes, particularly after salvage SBRT (sSBRT) following conventional irradiation, are scarce. OBJECTIVE: To investigate surgical specimens after sSBRT and primary SBRT (pSBRT) regarding histopathological changes. METHODS: We assessed 704 patients treated with spine SBRT 2006 to 2012. Thirty patients underwent salvage surgery; 23 histopathological reports were available. Clinical and histopathological findings were analyzed for sSBRT (69.6%) and pSBRT (30.4%). RESULTS: Mean time to surgery after sSBRT/pSBRT was 8.3/10.3 mo (P = .64). Reason for surgery included pain (sSBRT/pSBRT: 12.5%/71.4%, P = .25), fractures (sSBRT/pSBRT: 37.5%/28.6%, P = .68), and neurological symptoms (sSBRT/pSBRT: 68.8%/42.9%, P = .24). Radiological tumor progression after sSBRT/pSBRT was seen in 71.4%/42.9% (P = .2). Most specimens displayed viable/proliferative tumor (sSBRT/pSBRT: 62.5%/71.4%, P = .68 and 56.3%/57.1%, P = .97). Few specimens showed soft tissue necrosis (sSBRT/pSBRT: 20%/28.6%, P = .66), osteonecrosis (sSBRT/pSBRT: 14.3%/16.7%, P = .89), or bone marrow fibrosis (sSBRT/pSBRT: 42.9%/33.3%, P = .69). Tumor bed necrosis was more common after sSBRT (81.3%/42.9%, P = .066). Radiological tumor progression correlated with viable/proliferative tumor (P = .03/P = .006) and tumor bed necrosis (P = .03). Fractures were increased with bone marrow fibrosis (P = .07), but not with osteonecrosis (P = .53) or soft tissue necrosis (P = .19). Neurological symptoms were common with radiological tumor progression (P = .07), but not with fractures (P = .18). CONCLUSION: For both, sSBRT and pSBRT, histopathological changes were similar. Neurological symptoms were attributable to tumor progression and pathological fractures were not associated with osteonecrosis or tumor progression.

Risk for surgical complications after previous stereotactic body radiotherapy of the spine.

OBJECT: Stereotactic body radiotherapy (SBRT) for vertebral metastases has emerged as a promising technique, offering high rates of symptom relief and local control combined with low risk of toxicity. Nonetheless, local failure or vertebral instability may occur after spine SBRT, generating the need for subsequent surgery in the irradiated region. This study evaluated whether there is an increased incidence of surgical complications in patients previously treated with SBRT at the index level. METHODS: Based upon a retrospective international database of 704 cases treated with SBRT for vertebral metastases, 30 patients treated at 6 different institutions were identified who underwent surgery in a region previously treated with SBRT. RESULTS: Thirty patients, median age 59 years (range 27-84 years) underwent SBRT for 32 vertebral metastases followed by surgery at the same vertebra. Median follow-up time from SBRT was 17 months. In 17 cases, conventional radiotherapy had been delivered prior to SBRT at a median dose of 30 Gy in median 10 fractions. SBRT was administered with a median prescription dose of 19.3 Gy (range 15-65 Gy) delivered in median 1 fraction (range 1-17) (median EQD2/10 = 44 Gy). The median time interval between SBRT and surgical salvage therapy was 6 months (range 1-39 months). Reasons for subsequent surgery were pain (n = 28), neurological deterioration (n = 15) or fracture of the vertebral body (n = 13). Open surgical decompression (n = 24) and/or stabilization (n = 18) were most frequently performed; Five patients (6 vertebrae) were treated without complications with vertebroplasty only. Increased fibrosis complicating the surgical procedure was explicitly stated in one surgical report. Two durotomies occurred which were closed during the operation, associated with a neurological deficit in one patient. Median blood loss was 500 ml, but five patients had a blood loss of more than 1 l during the procedure. Delayed wound healing was reported in two cases. One patient died within 30 days of the operation. CONCLUSION: In this series of surgical interventions following spine SBRT, the overall complication rate was 19%, which appears comparable to primary surgery without previous SBRT. Prior spine SBRT does not appear to significantly increase the risk of intra- and post-surgical complications.

Seven-Year Outcomes Following Accelerated Partial Breast Irradiation Stratified by ASTRO Consensus Groupings.

OBJECTIVES: Limited long-term data exist regarding outcomes for patients treated with accelerated partial breast irradiation (APBI), particularly, when stratified by American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) risk groups. The purpose of this analysis is to present 5- and 7-year outcomes following APBI based on CS groupings. MATERIALS AND METHODS: A total of 690 patients with early-stage breast cancer underwent APBI from 1993 to 2012, receiving interstitial brachytherapy (n=195), balloon-based brachytherapy (n=290), or 3-dimensional conformal radiotherapy (n=205) at a single institution. Patients were stratified into suitable, cautionary, and unsuitable groups with 5-year outcomes analyzed. Seven-year outcomes were analyzed for a subset with follow-up of ≥2 years (n=625). RESULTS: Median follow-up was 6.7 years (range, 0.1 to 20.1 y). Patients assigned to cautionary and unsuitable categories were more likely to have high-grade tumors (21% to 25% vs. 9%, P=0.001), receive chemotherapy (15% to 38% vs. 6%, P<0.001), and have close/positive margins (9% to 11% vs. 0%, P<0.001). There was no difference in ipsilateral breast tumor recurrence at 5 or 7 years: 2.2%, 1.2%, 2.8% at 5 years (P=0.57), and 2.2%, 1.9%, 4.6% at 7 years (P=0.58) in the suitable, cautionary, and unsuitable groups, respectively. As compared with the suitable group, increased rates of distant metastases were noted for the unsuitable and cautionary groups at 5 years (P=0.04). CONCLUSIONS: No differences in rates of ipsilateral breast tumor recurrence were seen at 5 or 7 years when stratified by ASTRO CS groupings. Modest increases in distant recurrence were noted in the cautionary and unsuitable groups. These findings suggest that the ASTRO CS groupings stratify more for systemic recurrence and may not appropriately select patients for whole versus partial breast irradiation.

Vertebral compression fractures after stereotactic body radiation therapy: a large, multi-institutional, multinational evaluation.

OBJECTIVE The purpose of this study was to identify factors contributing to an increased risk for vertebral compression fracture (VCF) following stereotactic body radiation therapy (SBRT) for spinal tumors. METHODS A total of 594 tumors were treated with spinal SBRT as primary treatment or re-irradiation at 8 different institutions as part of a multi-institutional research consortium. Patients underwent LINAC-based, image-guided SBRT to a median dose of 20 Gy (range 8-40 Gy) in a median of 1 fraction (range 1-5 fractions). Median patient age was 62 years. Seventy-one percent of tumors were osteolytic, and a preexisting vertebral compression fracture (VCF) was present in 24% of cases. Toxicity was assessed following treatment. Univariate and multivariate analyses were performed using a logistic regression method to determine parameters predictive for post-SBRT VCF. RESULTS At a median follow-up of 10.1 months (range 0.03-57 months), 80% of patients had local tumor control. At the time of last imaging follow-up, at a median of 8.8 months after SBRT, 3% had a new VCF, and 2.7% had a progressive VCF. For development of any (new or progressive) VCF following SBRT, the following factors were predictive for VCF on univariate analysis: short interval from primary diagnosis to SBRT (less than 36.8 days), solitary metastasis, no additional bone metastases, no prior chemotherapy, preexisting VCF, no MRI used for target delineation, tumor volume of 37.3 cm(3) or larger, equivalent 2-Gy-dose (EQD2) tumor of 41.8 Gy or more, and EQD2 spinal cord Dmax of 46.1 Gy or more. Preexisting VCF, solitary metastasis, and prescription dose of 38.4 Gy or more were predictive on multivariate analysis. The following factors were predictive of a new VCF on univariate analysis: solitary metastasis, no additional bone metastases, and no MRI used for target delineation. Presence of a solitary metastasis and lack of MRI for target delineation remained significant on multivariate analysis. CONCLUSIONS A VCF following SBRT is more likely to occur following treatment for a solitary spinal metastasis, reflecting a more aggressive treatment approach in patients with adequately controlled systemic disease. Higher prescription dose and a preexisting VCF also put patients at increased risk for post-SBRT VCF. In these patients, pre-SBRT cement augmentation could be considered to decrease the risk of subsequent VCF.

Outcomes Associated With 3 Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer.

PURPOSE: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer. METHODS AND MATERIALS: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0. The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ(2) test. P values <.05 were considered significant. RESULTS: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years. CONCLUSIONS: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer.

Brachytherapy-based Accelerated Partial Breast Irradiation Provides Equivalent 10-Year Outcomes to Whole Breast Irradiation: A Matched-Pair Analysis.

INTRODUCTION: Although whole breast irradiation (WBI) represents the standard radiotherapy technique in breast conserving therapy, accelerated partial breast irradiation (APBI) has emerged as an option to reduce treatment duration with comparable clinical outcomes. The purpose of this analysis is to present long-term clinical outcomes between WBI and APBI. METHODS: A total of 3009 patients were treated with breast conserving therapy at a single institution between 1980 and 2012. Among them, 2528 patients received WBI and 481 received APBI (interstitial or balloon based). A matched-pair analysis was performed with patients matched by age (±3 years), stage (T-stage vs. T1 vs. T2), and estrogen receptor status (+/-). All patients had a minimum of 12 months follow-up. A total of 274 matches (ratio 1:1) were made. RESULTS: No differences between groups were noted with respect to clinicopathologic features; WBI patients demonstrated a trend for slightly larger tumors (1.3 vs. 1.1 cm, P=0.06). At 10 years, no differences were noted with respect to rates of ipsilateral breast tumor recurrence (4% vs. 4%, P=0.11), regional recurrence (1% vs. 1%, P=0.20), contralateral breast failure (9% vs. 3%, P=0.06), or distant metastases (3% vs. 6%, P=0.47) for WBI and APBI, respectively. In addition, 10-year disease-free survival (93% vs. 91%, P=0.10) and overall survival (83% vs. 75%, P=0.34) were similar. Long-term cosmesis was good to excellent in 94% of WBI patients versus 95% of APBI patients (P=0.78). CONCLUSIONS: At 10 years, no differences in recurrence or survival were found between patients undergoing WBI or brachytherapy-based APBI.

Comparison of chronic toxicities between brachytherapy-based accelerated partial breast irradiation and whole breast irradiation using intensity modulated radiotherapy.

PURPOSE: Brachytherapy-based APBI (bAPBI) shortens treatment duration and limits dose to normal tissue. While studies have demonstrated similar local control when comparing bAPBI and whole breast irradiation using intensity modulated radiotherapy (WBI-IMRT), comparison of late side effects is limited. Here, we report chronic toxicity profiles associated with these two treatment modalities. METHODS: 1034 patients with early stage breast cancer were treated at a single institution; 489 received standard-fractionation WBI-IMRT between 2000 and 2013 and 545 received bAPBI (interstitial 40%, applicator-based 60%) between 1993 and 2013. Chronic toxicity was evaluated ≥6 months utilizing CTCAE version 3.0; cosmesis was evaluated using the Harvard scale. RESULTS: Median follow-up was 4.6 years (range 0.1-13.4) for WBI-IMRT versus 6.7 years (range 0.1-20.1) for bAPBI (p < 0.001). Compared to WBI-IMRT, bAPBI was associated with higher rates of ≥grade 2 seroma formation (14.4% vs 2.9%, p < 0.001), telangiectasia (12.3% vs 2.1%, p = 0.002) and symptomatic fat necrosis (10.2% vs 3.6%, p < 0.001). Lower rates of hyperpigmentation were observed (5.8% vs 14.5%; p = 0.001). Infection rates were similar (3.3% vs 1.3%, p = 0.07). There was no difference between rates of fair (6.1% vs. 4.1%, p = 0.30) or poor (0.2% vs. 0.5%, p = NS) cosmesis. Mastectomy rates for local recurrence (3.1% for WBI-IMRT and 1.2% for bAPBI, p = 0.06), or for other reasons (0.8% and 0.6%, p = 0.60) were similar between groups. CONCLUSION: With 5-year follow-up, WBI-IMRT and bAPBI are associated with similar, acceptable rates of toxicity. These data further support the utilization of bAPBI as a modality to deliver adjuvant radiation in a safe and efficacious manner.

Combination therapy improves prostate cancer survival for patients with potentially lethal prostate cancer: The impact of Gleason pattern 5.

PURPOSE: To investigate the impact of Gleason pattern 5 (GP5) prostate cancer after either external beam radiotherapy (EBRT) or the combination of EBRT with low-dose rate brachytherapy boost (combo). METHODS AND MATERIALS: Between 1998 and 2008, 467 patients with National Comprehensive Cancer Network high-risk prostate cancer were treated with EBRT (n = 326) or combo (low-dose rate to 90-108 Gy using I-125 followed by EBRT) (n = 141). Freedom from biochemical failure, freedom from metastasis (FFM), cancer-specific survival (CSS), and overall survival were evaluated. RESULTS: Combo patients were younger (66 vs. 72 years, p < 0.001) and had fewer comorbidities (Charlson comorbidity index 3.7 vs. 4.4, p < 0.001). EBRT patients had higher tumor stages (T3-4: 30% vs. 21%, p = 0.03) and lower Gleason scores (8-10: 61% vs. 75%, p = 0.01). Androgen deprivation therapy use was similar between cohorts (85% vs. 87%, p = 0.5), but EBRT patients had longer androgen deprivation therapy use (median 14 vs. 12 months, p = 0.05). GP5 predicted worse FFM (p < 0.001, hazard ratio [HR] 3.3, 95% confidence interval [CI]1.8-6.2]) and CSS (p < 0.001, HR 5.9, 95% CI 2.7-12.9) for the EBRT group, but not for the combo group (p = 0.86, HR 0.48, 95% CI 0.1-2.4 for metastasis and p = 0.5, HR 1.6, 95% CI 0.33-8.0 for CSS). In those with GP5 (n = 143), combo was associated with improved outcomes in all endpoints. On univariate analysis, 5-year outcomes for combo vs. EBRT were as follows: freedom from biochemical failure 89% vs. 65%, FFM 89% vs. 67%, CSS 93% vs. 78%, and overall survival 88% vs. 67% (p < 0.05 for all). CONCLUSION: Combo was associated with improved outcomes for men with GP5 prostate cancer. This highlights the importance of local therapy, especially in patients with the highest pathologic grade disease.

Dosimetric evaluation of target coverage as a predictor of local failure following stereotactic body radiation therapy for spinal tumors.

PURPOSE: To perform a dosimetric analysis of target coverage and determine parameters predictive for local failure (LF) in patients undergoing spinal stereotactic body radiation therapy (sSBRT).Materials and Methods: Sixty-seven spinal tumors in 59 patients were treated with image-guided linac-based sSBRT from 2008-2012. Median prescription dose was 18Gy (8-35) delivered in 1-5 fractions (87% single-fraction). Prescription dose was targeted to cover ≥ 80% of PTV within spinal cord (SC) dose constraints (9/11Gy to 0.1cc SC/SC+2mm). Twelve tumors had local failure (LF, median time-to-failure 3.7 months) and were compared to 14 tumors with >1-year follow-up and local control (LC). Univariate and multivariate analyses were performed to determine parameters predictive of LF. RESULTS: Median follow-up was 7.4 months and 24.7 months for LF and LC, respectively. Post-SBRT, 42% of LF patients had neurological symptoms due to tumor progression. No patients developed post-SBRT myelopathy. Pre-treatment PTV volumes were not statistically different (median/mean/range 61.8/74.5/19.9-206.4cc for LF vs 39.4/47.1/10.3-119.7cc for LC; p=0.13). LF tumors had larger volumes receiving <80% of prescription dose (5.2cc vs 1.9cc, p=0.02) and larger overlap volume between GTV/SC within 2 and 3mm (p=0.01/p=0.007). LF tumors had lower GTV minimum dose (5.6 vs 8.5Gy, p=0.001) and smaller GTV to SC distance (0.06 vs 0.19mm, p=0.049). Maximum SC doses were not statistically different (6.4Gy LC vs 9.2Gy LF, p=0.33). GTV minimum dose was predictive of LF, with a trend for overlapping GTV/SC volume within 2mm. CONCLUSIONS: Minimum GTV dose, PTV volume receiving <80% prescription dose, smaller GTV-SC distance, and large overlapping volume of PTV/SC are predictive of LF after SBRT. Given the absence of SC toxicity but neurological progression upon LF, less conservative SC constraints should be considered.