MRI Response to Pre-operative Stereotactic Ablative Body Radiotherapy (SABR) in Early Stage ER/PR+ HER2- Breast Cancer correlates with Surgical Pathology Tumor Bed Cellularity.

OBJECTIVE: This study evaluates breast MRI response of ER/PR+ HER2- breast tumors to pre-operative SABR with pathologic response correlation. METHODS: Women enrolled in a phase 2 single institution trial of SABR for ER/PR+ HER2- breast cancer were retrospectively evaluated for radiologic-pathologic correlation of tumor response. These patients underwent baseline breast MRI, SABR (28.5 Gy in 3 fractions), follow-up MRI 5 to 6 weeks post-SABR, and lumpectomy. Tumor size and BI-RADS descriptors on pre and post-SABR breast MRIs were compared to determine correlation with surgical specimen % tumor cellularity (%TC). Reported MRI tumor dimensions were used to calculate percent cubic volume remaining (%VR). Partial MRI response was defined as a BI-RADs descriptor change or %VR ≤ 70%, while partial pathologic response (pPR) was defined as %TC ≤ 70%. RESULTS: Nineteen patients completed the trial, and %TC ranged 10% to 80%. For BI-RADS descriptor analysis, 12 of 19 (63%) showed change in lesion or kinetic enhancement descriptors post-SABR. This was associated with lower %TC (29% vs. 47%, P = .042). BI-RADS descriptor change analysis also demonstrated high PPV (100%) and specificity (100%) for predicting pPR to treatment (sensitivity 71%, accuracy 74%), but low NPV (29%). MRI %VR demonstrated strong linear correlation with %TC (R = 0.70, P < .001, Pearson's Correlation) and high accuracy (89%) for predicting pPR (sensitivity 88%, specificity 100%, PPV 100%, and NPV 50%). CONCLUSION: Evaluating breast cancer response on MRI using %VR after pre-operative SABR treatment can help identify patients benefiting the most from neoadjuvant radiation treatment of their ER/PR+ HER2- tumors, a group in which pCR to neoadjuvant therapy is rare.

Clinical characteristics and prognostic factors of 70 patients with Sézary syndrome: a single-institutional experience at Moffitt cancer center.

Sézary syndrome (SS) is a rare and aggressive leukemic variant of cutaneous T-cell lymphoma, with a median overall survival (OS) rate of 2-4 years. Few studies have described the clinical outcome of SS patients since 2012. We retrospectively analyzed 70 patients diagnosed with SS treated at a high-volume tertiary cancer center between 2000 and 2018. Overall survival at 1 and 5 years was 84.1% and 50.7%, respectively. Univariate analyses identified older age (>65 years) and male sex as poor prognostic factors. Five patients presented with circulating large granular lymphocytic proliferation and had a favorable prognosis. Targeted therapies were effective in treating refractory/relapsed SS patients with a durable response. Therapeutic advancements and the comprehensive treatments used in a multidisciplinary clinic improved OS rates.

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Objective: To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR). Methods: Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer. MRI analysis was performed on DCE T1-weighted images. MRI voxels were assigned eight habitats based on high (H) or low (L) maximum enhancement and the sequentially numbered dynamic sequence of maximum enhancement (H1-4, L1-4). MRI response was analyzed by percent tumor volume remaining (%VR = volume post-SABR/volume pre-SABR), and percent habitat makeup (%HM of habitat X = habitat X voxels/total voxels in the segmented volume). These were correlated with percent tumor bed cellularity (%TC) for pathologic response. Results: Sixteen patients completed the trial. The %TC ranged 20%-80%. MRI %VR demonstrated strong correlations with %TC (Pearson R = 0.7-0.89). Pre-SABR tumor %HMs differed significantly from whole breasts (P = 0.005 to <0.00001). Post-SABR %HM of tumor habitat H4 demonstrated the largest change, increasing 13% (P = 0.039). Conversely, combined %HM for H1-3 decreased 17% (P = 0.006). This change correlated with %TC (P < 0.00001) and distinguished pathologic partial responders (≤70 %TC) from nonresponders with 94% accuracy, 93% sensitivity, 100% specificity, 100% positive predictive value, and 67% negative predictive value. Conclusion: In patients undergoing preoperative SABR treatment for ER/PR+ HER2- breast cancer, quantitative MRI habitat analysis of %VR and %HM change correlates with pathologic response.

Stage IIIC endometrial cancer review: Current controversies in adjuvant therapy.

Stage IIIC is the most common stage of locally advanced sub-stage of endometrial cancer, nevertheless, the optimal management for these patients remains controversial. Adjuvant chemotherapy alone more effectively suppressed distant metastases but resulted in a higher rate of pelvic failure, while adjuvant radiation more effectively controlled pelvic recurrences but was associated with more frequent distant metastases. Two recent randomized trials, PORTEC3 and GOG 258, each have attempted to integrate multimodal therapy. However, heterogeneous cohorts analyzed together, including high risk stage I, stage III and stage IV, limit our ability to make conclusions specific to stage IIIC disease. Here, we review clinical evidence pertaining to management and outcomes with stage IIIC uterine carcinoma with brief discussion on evolving approaches. The studies reviewed demonstrate for stage IIIC disease radiation improves local control but does not confer an overall survival benefit and chemotherapy can improve overall survival. The data seem to suggest that aside from the possibility of defining subgroups that may confer an overall survival benefit from combined modality therapy, the future to improving survival lies in the exploration of better therapeutic regimens that will result from tailored biomarker-based therapy.

Comparison of Definitive Cervical Cancer Management With Chemotherapy and Radiation Between Two Centers With Variable Resources and Opportunities for Improved Treatment.

PURPOSE: Cervical cancer remains a major health challenge in low- to middle-income countries. We present the experiences of two centers practicing in variable resource environments to determine predictors of improved radiochemotherapy treatment. METHODS AND MATERIALS: This comparative review describes cervical cancer presentation and treatment with concurrent chemoradiotherapy with high-dose-rate brachytherapy between 2014 and 2017 at the National Radiotherapy Oncology and Nuclear Medicine Center (NRONMC) in Korle-Bu Teaching Hospital, Accra, Ghana, and Moffitt Cancer Center (MCC), Tampa, FL. RESULTS: Median follow-up for this study was 16.9 months. NRONMC patients presented with predominantly stage III disease (42% v 16%; P = .002). MCC patients received para-aortic node irradiation (16%) and interstitial brachytherapy implants (19%). Median treatment duration was longer for NRONMC patients compared with MCC patients (59 v 52 days; P < .0001), and treatment duration ≥ 55 days predicted worse survival on multivariable analysis (MVA; P = .02). Stage ≥ III disease predicted poorer local control on MVA. There was a difference in local control among patients with stage III disease (58% v 91%; P = .03) but not in survival between MCC and NRONMC. No significant difference in local control was observed for stage IB, IIA, and IIB disease. CONCLUSION: Although there were significant differences in disease presentation between the two centers, treatment outcomes were similar for patients with early-stage disease. Longer treatment duration and stage ≥ III disease predicted poor outcomes.

Prostatic Artery Embolization Is Safe and Effective for Medically Recalcitrant Radiation-Induced Prostatitis.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents 90% of all chronic prostatitis cases and may occur after radiation therapy (RT) for localized prostate cancer. Medical therapy is effective in approximately 50% of cases, with no therapy demonstrating consistent efficacy in refractory cases. Prostatic artery embolization (PAE) is effective in men with lower urinary tract symptoms and benign prostatic hyperplasia. We report clinical improvement after PAE in a case series of men with CP/CPPS after RT. METHODS AND MATERIALS: Nine men (median age 72 years; range, 61-83 years) with CP/CPPS after RT for prostate cancer underwent PAE. Baseline International Prostate Symptom Score was recorded in 5 patients (median 23; range, 4-26), Chronic Prostatitis Symptom Index score in 6 patients (median 22.5; range, 6-34), and quality of life (QoL) score in 8 patients (median 5; range, 2-6). Median baseline prostate volume was 49 cm3 (range, 22-123 cm3). Patients were followed up at 6 and 12 weeks with QoL, International Prostate Symptom Score, and/or Chronic Prostatitis Symptom Index score and magnetic resonance imaging. RESULTS: Technical success (ie, bilateral embolization) was achieved in 78% (n = 7) of patients with the other 2 patients having undergone unilateral embolization with no major complications. Clinical success was seen in 89% (n = 8) of patients and QoL improved in 78% (n = 7) during the follow-up period. CONCLUSION: CP/CPPS after RT for localized prostate cancer is a highly morbid condition, with medical therapy successful in only 50% of cases. PAE may be a successful therapy for medically recalcitrant CP/CPPS, and further studies are necessary to understand the best patient selection and scenario for PAE in the setting of CP/CPPS.

Using the Radiosensitivity Index (RSI) to Predict Pelvic Failure in Endometrial Cancer Treated With Adjuvant Radiation Therapy.

PURPOSE: Variability exists in the adjuvant treatment for endometrial cancer (EC) based on surgical pathology and institutional preference. The radiosensitivity index (RSI) is a previously validated multigene expression index that estimates tumor radiosensitivity. We evaluate RSI as a genomic predictor for pelvic failure (PF) in EC patients treated with adjuvant radiation therapy (RT). METHODS AND MATERIALS: Using our institutional tissue biorepository, we identified EC patients treated between January 1999 and April 2011 with primarily endometrioid histology (n = 176; 86%) who received various adjuvant therapies. The RSI 10-gene signature was calculated for each sample using the previously published algorithm. Radiophenotype was determined using the previously identified cutpoint where RSI ≥ 0.375 denotes radioresistance (RR) and RSI < 0.375 describes radiosensitivity. RESULTS: A total of 204 patients were identified, of which 83 (41%) were treated with adjuvant RT. Median follow-up was 38.5 months. All patients underwent hysterectomy with bilateral salpingo-oophorectomy with the majority undergoing lymph node dissection (n = 181; 88%). In patients treated with radiation, RR tumors were more likely to experience PF (3-year pelvic control 84% vs 100%; P = .02) with worse PF-free survival (PFFS) (3-year PFFS 65% vs 89%; P = .04). Furthermore, in the patients who did not receive RT, there was no difference in PF (P = .87) or PFFS (P = .57) between the RR/radiosensitive tumors. On multivariable analysis, factors that continued to predict for PF included the RR phenotype (hazard ratio [HR], 12.2; P = .003), lymph node involvement (HR, 4.4; P = .02), and serosal or adnexal involvement (HR, 5.3; P = .01). CONCLUSIONS: On multivariable analysis, RSI was found to be a significant predictor of PF in patients treated with adjuvant RT. We propose using RSI to predict which patients are at higher risk for failing in the pelvis and may be candidates for treatment escalation in the adjuvant setting.

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity.

INTRODUCTION: To evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. METHODS: In this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. RESULTS: Twenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3-52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2-44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3-4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3-4 toxicity. CONCLUSION: High-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

Radiotherapy for early stage diffuse large B-cell lymphoma with or without double or triple hit genetic alterations.

We investigated whether adding radiation (RT) to systemic therapy improved outcomes in early stage diffuse large B-cell lymphoma (DLBCL) patients with or without double- or triple-hit lymphoma (DHL/THL) biology. This analysis included 183 patients profiled with fluorescent in situ hybridization (FISH) for alterations in MYC, BLC2, and/or BCL6. A total of 146 (80%) were non-DHL/THL, 27 (15%) were DHL, and 10 (6%) were THL. Systemic therapy without RT resulted in inferior freedom from relapse (FFR) (HR: 2.28; 95% CI, 1.10-4.77; p = .02). The median FFR for non-DHL/THL was not reached and was 33 and 22.3 months for DHL and THL, respectively; p < .001. Low-risk (R-IPI <2) DHL/THL patients treated with rituximab-based therapy had 3-year FFR rates of 11% and 71% for systemic therapy without and with RT, respectively; p = .04. No differences in overall survival were observed between the treatment groups. Treatment intensification with RT may improve early stage DHL/THL outcomes.

Personalizing Radiation Treatment Delivery in the Management of Breast Cancer.

Long-term data establishes the efficacy of radiotherapy in the adjuvant management of breast cancer. New dose and fractionation schemas have evolved and are available, each with unique risks and rewards. Current efforts are ongoing to tailor radiotherapy to the unique biology of breast cancer. In this review, we discuss our efforts to personalize radiotherapy dosing using genomic data and the implications for future clinical trials. We also explore immune mechanisms that may contribute to a tumor's unique radiation sensitivity or resistance.

Reproducibility of F18-FDG PET radiomic features for different cervical tumor segmentation methods, gray-level discretization, and reconstruction algorithms.

Site-specific investigations of the role of radiomics in cancer diagnosis and therapy are emerging. We evaluated the reproducibility of radiomic features extracted from 18 Flourine-fluorodeoxyglucose (18 F-FDG) PET images for three parameters: manual versus computer-aided segmentation methods, gray-level discretization, and PET image reconstruction algorithms. Our cohort consisted of pretreatment PET/CT scans from 88 cervical cancer patients. Two board-certified radiation oncologists manually segmented the metabolic tumor volume (MTV1 and MTV2 ) for each patient. For comparison, we used a graphical-based method to generate semiautomated segmented volumes (GBSV). To address any perturbations in radiomic feature values, we down-sampled the tumor volumes into three gray-levels: 32, 64, and 128 from the original gray-level of 256. Finally, we analyzed the effect on radiomic features on PET images of eight patients due to four PET 3D-reconstruction algorithms: maximum likelihood-ordered subset expectation maximization (OSEM) iterative reconstruction (IR) method, fourier rebinning-ML-OSEM (FOREIR), FORE-filtered back projection (FOREFBP), and 3D-Reprojection (3DRP) analytical method. We extracted 79 features from all segmentation method, gray-levels of down-sampled volumes, and PET reconstruction algorithms. The features were extracted using gray-level co-occurrence matrices (GLCM), gray-level size zone matrices (GLSZM), gray-level run-length matrices (GLRLM), neighborhood gray-tone difference matrices (NGTDM), shape-based features (SF), and intensity histogram features (IHF). We computed the Dice coefficient between each MTV and GBSV to measure segmentation accuracy. Coefficient values close to one indicate high agreement, and values close to zero indicate low agreement. We evaluated the effect on radiomic features by calculating the mean percentage differences (d¯) between feature values measured from each pair of parameter elements (i.e. segmentation methods: MTV1 -MTV2 , MTV1 -GBSV, MTV2 -GBSV; gray-levels: 64-32, 64-128, and 64-256; reconstruction algorithms: OSEM-FORE-OSEM, OSEM-FOREFBP, and OSEM-3DRP). We used |d¯| as a measure of radiomic feature reproducibility level, where any feature scored |d¯| ±SD ≤ |25|% ± 35% was considered reproducible. We used Bland-Altman analysis to evaluate the mean, standard deviation (SD), and upper/lower reproducibility limits (U/LRL) for radiomic features in response to variation in each testing parameter. Furthermore, we proposed U/LRL as a method to classify the level of reproducibility: High- ±1% ≤ U/LRL ≤ ±30%; Intermediate- ±30% < U/LRL ≤ ±45%; Low- ±45 < U/LRL ≤ ±50%. We considered any feature below the low level as nonreproducible (NR). Finally, we calculated the interclass correlation coefficient (ICC) to evaluate the reliability of radiomic feature measurements for each parameter. The segmented volumes of 65 patients (81.3%) scored Dice coefficient >0.75 for all three volumes. The result outcomes revealed a tendency of higher radiomic feature reproducibility among segmentation pair MTV1 -GBSV than MTV2 -GBSV, gray-level pairs of 64-32 and 64-128 than 64-256, and reconstruction algorithm pairs of OSEM-FOREIR and OSEM-FOREFBP than OSEM-3DRP. Although the choice of cervical tumor segmentation method, gray-level value, and reconstruction algorithm may affect radiomic features, some features were characterized by high reproducibility through all testing parameters. The number of radiomic features that showed insensitivity to variations in segmentation methods, gray-level discretization, and reconstruction algorithms was 10 (13%), 4 (5%), and 1 (1%), respectively. These results suggest that a careful analysis of the effects of these parameters is essential prior to any radiomics clinical application.

Frequency of whole breast radiation therapy after intraoperative radiation therapy due to criteria identified by lumpectomy.

PURPOSE: For selected early breast cancers, intraoperative radiation therapy (IORT) at the time of lumpectomy can be an efficient alternative to fractionated whole breast radiation therapy (WBRT). However, some patients are later recommended WBRT after IORT due to surgical pathologic findings. To understand risk factor identification rates triggering WBRT recommendation, we analyzed adverse prognostic features based on multiple international criteria for suitability for accelerated partial breast irradiation. METHODS AND MATERIALS: We performed a single-institution retrospective review of all 200 nonrecurrent invasive breast carcinomas that received IORT in 20 Gy to the tumor cavity using a 50 kV photon applicator between January 2011 and December 2015. IORT eligibility was based on the 2009 accelerated partial breast irradiation Consensus Statement from the American Society for Radiation Oncology (ASTRO). IORT was offered as the sole radiation modality to patients meeting 0-1 "cautionary" and no "unsuitable" criteria before lumpectomy. WBRT was recommended after IORT when 2+ cautionary and/or 1+ unsuitable criteria were met after accounting for resection pathology. We recalculated WBRT recommendation rates using initial and reresection margins for ASTRO consensus, Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations, and TARGeted Intraoperative radioTherapy vs. Postoperative Radiotherapy trial "prepathology" stratum protocol. RESULTS: Depending on the selection criteria chosen, rates of WBRT recommendation can vary from 4.5% to 33%. CONCLUSIONS: WBRT recommendation rates of 30-33% after lumpectomy and IORT are observed when the WBRT indication is a single ASTRO cautionary/unsuitable, Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology intermediate/high-risk criterion, or TARGeted Intraoperative radioTherapy vs. postoperative radiotherapy trial protocol recommendation. Alternatively, allowing for re-excision to clear margins and accepting one ASTRO cautionary factor lowered the rate of WBRT recommendation to 9.5%.

IMRT with simultaneous integrated boost and concurrent chemotherapy for locoregionally advanced squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. METHODS AND MATERIALS: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. RESULTS: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. CONCLUSIONS: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

Current challenges in clinical management of endometrial cancer.

Endometrial cancer remains a management challenge. Improved understanding of the mechanisms of carcinogenesis may enable better understanding of biologic behavior and guide therapy. Improvements in diagnostic imaging, radiation delivery systems, and systemic therapies potentially can improve outcomes while minimizing morbidity. Novel strategies for screening and prevention also hold promise for reducing incidence and mortality of this disease.

Treatment of intermediate-risk prostate cancer with brachytherapy without supplemental pelvic radiotherapy: a review of the H. Lee Moffitt Cancer Center experience.

PURPOSE: To determine the biochemical outcomes of patients with intermediate-risk prostate cancer treated at the H. Lee Moffitt Cancer Center with an I-125 permanent seed implant without supplemental pelvic radiotherapy. METHODS AND MATERIALS: Under an institutional review board approved protocol, the charts of 88 patients with intermediate-risk prostate cancer and a minimum follow-up of 36 months treated with brachytherapy without supplemental pelvic radiotherapy were reviewed. Median follow-up for the whole cohort was 57 months (range 37-121). Biochemical failure was defined using the American Society for Therapeutic Radiology and Oncology definition. RESULTS: The 5-year biochemical failure-free survival for the cohort was 83%. Patients with perineural invasion had a worse biochemical outcome, which was statistically significant (perineural invasion vs. no perineural invasion, 5-year biochemical failure-free survival 64% vs. 89%, P = 0.004). None of the following factors were found significant in this subset of patients: Gleason scores 6 versus 7, primary Gleason grades 3 versus 4, percentage of core positive <20% versus >20%, number of cores positive <2 versus 2 versus >2, hormonal therapy versus no hormonal therapy, T1 versus T2, prostate-specific antigen <10 versus >10, or > or =2 intermediate risk factors versus 1 intermediate risk factor. CONCLUSIONS: Our data suggest that patients with intermediate-risk prostate cancer may be treated effectively with brachytherapy without supplemental pelvic radiotherapy. However, because of the limited nature of our study, we cannot exclude that patients with intermediate-risk prostate cancer may benefit from supplemental external beam radiotherapy.