Christine Chin

Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy.

PURPOSEnTo compare the efficacy of dolasetron and ondansetron in controlling nausea and vomiting in the first 24 hours; to evaluate the efficacy when dexamethasone is added to either drug in the first 24 hours; and to extend these comparisons over 7 days in patients receiving moderately emetogenic chemotherapy.nnnPATIENTS AND METHODSnThis was a multicenter, double-blind, randomized study with six parallel arms that used a 2 x 2 factorial design in chemotherapy-naive patients. In arm 1, dolasetron (2.4 mg/kg) was given intravenously (I.V.) prechemotherapy, followed 24 hours later by oral dolasetron (200 mg once daily) for 6 days. Arms 2 and 3 consisted of dolasetron and dexamethasone 8 mg I.V., followed 24 hours later by oral dexamethasone (8 mg once daily) in one arm, and oral dexamethasone and dolasetron in the other, also for 6 days. In arms 4, 5, and 6, ondansetron (32 mg I.V. or 8 mg orally twice daily) was administered in a similar manner to arms 1, 2, and 3 before and 24 hours after chemotherapy. Mean nausea severity (MNS) was assessed on a visual analog scale (VAS) in a daily diary.nnnRESULTSnOf 703 patients enrolled, 696 were eligible. There were 343 dolasetron- and 353 ondansetron-treated patients; 57% of dolasetron-treated patients had complete protection in the first 24 hours versus 67% of patients who received ondansetron (P = .013). MNS was also more pronounced on the dolasetron arm (P = .051). Sixty-seven percent of patients who received added dexamethasone in the first 24 hours had complete protection, compared with 55% without dexamethasone (P < .001). MNS was significantly reduced with the addition of dexamethasone (P < .001). At 7 days, dolasetron and ondansetron had equivalent complete protection rates (36% and 39%, respectively). With the addition of dexamethasone, 48% of patients compared with 28% had complete protection (P < .001). MNS was significantly improved with added dexamethasone (P < .001).nnnCONCLUSIONnAt the doses used, dolasetron was significantly less effective than ondansetron at controlling nausea and vomiting in the first 24 hours in patients receiving moderately emetogenic chemotherapy, but there was no demonstrable difference between both drugs over 7 days. The addition of dexamethasone significantly improved the efficacy of both drugs in the first 24 hours and over 7 days.

Evaluation of Partial Breast Reirradiation with Intraoperative Radiotherapy after Prior Thoracic Radiation: A Single-Institution Report of Outcomes and Toxicity

Introduction Mastectomy is the current standard of care for ipsilateral breast tumor recurrences after prior whole breast irradiation (WBI). We report our single-institution experience with breast-conserving surgery (BCS) followed by intraoperative radiotherapy (IORT) as an alternative to salvage mastectomy for new or recurrent breast cancers that develop in the setting of prior thoracic radiation. Methods We performed an IRB-approved retrospective review of patients treated with breast IORT between September 2013 and November 2016. We identified 12 patients who declined salvage mastectomy for their breast cancer after prior thoracic radiation. IORT was delivered using the Intrabeam™ device (Carl Zeiss, Germany). A dose of 20u2009Gy was prescribed to the lumpectomy cavity surface using 50u2009kV X-rays. We graded both acute and late treatment-related breast toxicities using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Local control, mastectomy-free survival, distant metastasis, and overall survival were determined. Results Our study included nine patients who developed a new or recurrent ipsilateral breast cancer after prior WBI for early-stage breast cancer, two patients with primary breast cancer after mantle-field radiation for Hodgkin’s lymphoma, and one patient with a synchronous stage III non-small cell lung cancer treated with definitive radiation to the ipsilateral lung and mediastinum. The median time from prior radiation to presentation was 18u2009years (range: 2u2009months to 46u2009years). All patients successfully underwent partial breast reirradiation with IORT and were able to preserve their breast. At a median follow-up of 14u2009months (4–25u2009months), there were no local or distant recurrences. There was a single non-cancer-related death. In the acute setting, we observed grade 1 toxicity in 58% (nu2009=u20097), grade 2 toxicity in 17% (nu2009=u20092), and no grade 3 or higher toxicity. In the late setting, at least 3u2009months after IORT, we observed grade 1 hyperpigmentation and/or fibrosis in 50% (nu2009=u20096), symptomatic seroma requiring drainage in 33% (nu2009=u20094). A single patient developed an abscess requiring hospitalization and intravenous antibiotic therapy. Conclusion BCS with IORT is a feasible salvage option for patients who present with localized breast cancer after prior thoracic radiation treatment. Continued follow-up of these patients is warranted given the incidence of delayed toxicity.

Expanding the Criteria for Nipple-Sparing Mastectomy in Patients With Poor Prognostic Features

Micro‐Abstract In many institutions, nipple‐sparing mastectomy (NSM) is reserved for prophylaxis or for early‐stage breast cancer. With increasing utility of neoadjuvant chemotherapy (NAC), patients with poor prognostic features may downstage significantly. In this retrospective review of our cohort of 63 patients who underwent NSM after NAC, prior breast surgery, or irradiation, we demonstrate oncologic safety while preserving cosmesis. Background: In this study we aimed to review the outcomes of nipple‐sparing mastectomy (NSM) in the setting of expanded criteria: previous breast surgery/irradiation, neoadjuvant chemotherapy (NAC), post‐NSM irradiation, and to assess conversion to acceptable criteria after NAC. Patients and Methods: In this single‐institution institutional review board‐approved retrospective review, we identified patients who underwent NSM after previous breast intervention or NAC from January 2010 to February 2017. Clinicopathologic features, previous breast surgeries, response rate, complications, and recurrences were recorded. Results: Sixty‐three patients underwent 106 NSMs. Among 63 patients, 39 (61.9%) received NAC, 30 (47.6%) previous lumpectomy, 4 (6.3%) with cosmetic implants, 4 (6.3%) with mastopexy, 5 (7.9%) with previous radiation therapy, and 21 (33%) underwent post‐NSM radiation therapy. Transient epidermolysis occurred in 24 patients (38.1%), with 16 patients (66.6%) having complete flap recovery and nipple loss in 8 patients (12.6%). All 10 patients with central disease on pre‐NAC imaging converted to acceptable criteria, with 9 having successful NSM. At mean 67.2‐month follow‐up, 56 patients (88.9%) were disease‐free, 5 (7.9%) experienced a systemic recurrence, and 2 (3.2%) a local recurrence. Conclusion: NSM is oncologically acceptable in this patient cohort. Patients with large central tumors who undergo NAC should be reconsidered after completion of chemotherapy because many might convert to successful nipple‐areolar preservation.

Prior to Initiation of Chemotherapy, Can We Predict Breast Tumor Response? Deep Learning Convolutional Neural Networks Approach Using a Breast MRI Tumor Dataset

We hypothesize that convolutional neural networks (CNN) can be used to predict neoadjuvant chemotherapy (NAC) response using a breast MRI tumor dataset prior to initiation of chemotherapy. An institutional review board-approved retrospective review of our database from January 2009 to June 2016 identified 141 locally advanced breast cancer patients who (1) underwent breast MRI prior to the initiation of NAC, (2) successfully completed adriamycin/taxane-based NAC, and (3) underwent surgical resection with available final surgical pathology data. Patients were classified into three groups based on their NAC response confirmed on final surgical pathology: complete (group 1), partial (group 2), and no response/progression (group 3). A total of 3107 volumetric slices of 141 tumors were evaluated. Breast tumor was identified on first T1 postcontrast dynamic images and underwent 3D segmentation. CNN consisted of ten convolutional layers, four max-pooling layers, and dropout of 50% after a fully connected layer. Dropout, augmentation, and L2 regularization were implemented to prevent overfitting of data. Non-linear functions were modeled by a rectified linear unit (ReLU). Batch normalization was used between the convolutional and ReLU layers to limit drift of layer activations during training. A three-class neoadjuvant prediction model was evaluated (group 1, group 2, or group 3). The CNN achieved an overall accuracy of 88% in three-class prediction of neoadjuvant treatment response. Three-class prediction discriminating one group from the other two was analyzed. Group 1 had a specificity of 95.1%u2009±u20093.1%, sensitivity of 73.9%u2009±u20094.5%, and accuracy of 87.7%u2009±u20090.6%. Group 2 (partial response) had a specificity of 91.6%u2009±u20091.3%, sensitivity of 82.4%u2009±u20092.7%, and accuracy of 87.7%u2009±u20090.6%. Group 3 (no response/progression) had a specificity of 93.4%u2009±u20092.9%, sensitivity of 76.8%u2009±u20095.7%, and accuracy of 87.8%u2009±u20090.6%. It is feasible for current deep CNN architectures to be trained to predict NAC treatment response using a breast MRI dataset obtained prior to initiation of chemotherapy. Larger dataset will likely improve our prediction model.

Velocity-based Adaptive Registration and Fusion for Fractionated Stereotactic Radiosurgery Using the Small Animal Radiation Research Platform

PURPOSEnTo implement Velocity-based image fusion and adaptive deformable registration to enable treatment planning for preclinical murine models of fractionated stereotactic radiosurgery (fSRS) using the small animal radiation research platform (SARRP).nnnMETHODS AND MATERIALSnC57BL6 mice underwent 3 unique cone beam computed tomography (CBCT) scans: 2 in the prone position and a third supine. A single T1-weighted post-contrast magnetic resonance imaging (MRI) series of a murine metastatic brain tumor model was selected for MRI-to-CBCT registration and gross tumor volume (GTV) identification. Two arms were compared: Arm 1, where we performed 3 individual MRI-to-CBCT fusions using rigid registration, contouring GTVs on each, and Arm 2, where the authors performed MRI-to-CBCT fusion and contoured GTV on the first CBCT followed by Velocity-based adaptive registration. The first CBCT and associated GTV were exported from MuriPlan (Xstrahl Life Sciences) into Velocity (Varian Medical Systems, Inc, Palo Alto, CA). In Arm 1, the second and third CBCTs were exported similarly along with associated GTVs (Arm 1), while in Arm 2, the first (prone) CBCT was fused separately to the second (prone) and third (supine) CBCTs, performing deformable registrations on initial CBCTs and applying resulting matrices to the contoured GTV. Resulting GTVs were compared between Arms 1 andxa02.nnnRESULTSnComparing GTV overlays using repeated MRI fusion and GTV delineation (Arm 1) versus those of Velocity-based CBCT and GTV adaptive fusion (Arm 2), mean deviationsxa0±xa0standard deviation in the axial, sagittal, and coronal planes were 0.46xa0±xa00.16, 0.46xa0±xa00.22, and 0.37xa0±xa00.22xa0mm for prone-to-prone and 0.52xa0±xa00.27, 0.52xa0±xa00.36, and 0.68xa0±xa00.31xa0mm for prone-to-supine adaptive fusions, respectively.nnnCONCLUSIONSnVelocity-based adaptive fusion of CBCTs and contoured volumes allows for efficient fSRS planning using a single MRI-to-CBCT fusion. This technique is immediately implementable on current SARRP systems, facilitating advanced preclinical treatment paradigms using existing clinical treatment planning software.

Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy

PurposeCapecitabine has been studied as a radiosensitizer, and our study seeks to examine the association of concurrent capecitabine/radiation therapy (RT) on event-free- (EFS) and overall survival (OS) in women with breast cancer (BC) with residual disease after neoadjuvant chemotherapy (NAC).Methods/patientsIn a retrospective study of women with BC who received adriamycin/taxane-based NAC from 2004–2016, we identified 21 women administered concurrent capecitabine/RT. To assess differences in survival, we selected a clinical control cohort (nu2009=u200957) based on criteria used to select patients for capecitabine/RT. We also created a matched cohort (2:1), matching on tumor subtype, pathological stage and age (<u200950 or 50+ years). Differences in EFS, using STEEP criteria, and OS, using all-cause mortality, between those who received capecitabine/RT and controls were assessed.ResultsOf the 21 women who received capecitabine/RT, median age was 52xa0years. The majority were pathologic stage III (nu2009=u200915) and hormone receptor-positive/HER2-negative BC (nu2009=u200920). In those receiving capecitabine/RT, there were 9 events, compared with 14 events in clinical and 10 events in matched controls. Capecitabine/RT was associated with worse OS in clinical (HR 3.83 95% CI 1.12–13.11, pu2009=u20090.03) and matched controls (HR 3.71 95% CI 1.04–13.18, pu2009=u20090.04), after adjusting for clinical size, pathological stage and lymphovascular invasion. Capecitabine/RT was also associated with a trend towards worse EFS in clinical (HR 2.41 95% CI 0.86–6.74, pu2009=u20090.09) and matched controls (HR 2.68 95% CI 0.91–7.90, pu2009=u20090.07) after adjustment.ConclusionConcurrent capecitabine/RT after NAC is associated with worse survival and should be carefully considered in BC.

Predicting Post Neoadjuvant Axillary Response Using a Novel Convolutional Neural Network Algorithm

ObjectivesIn the postneoadjuvant chemotherapy (NAC) setting, conventional radiographic complete response (rCR) is a poor predictor of pathologic complete response (pCR) of the axilla. We developed a convolutional neural network (CNN) algorithm to better predict post-NAC axillary response using a breast MRI dataset.MethodsAn institutional review board-approved retrospective study from January 2009 to June 2016 identified 127 breast cancer patients who: (1) underwent breast MRI before the initiation of NAC; (2) successfully completed Adriamycin/Taxane-based NAC; and (3) underwent surgery, including sentinel lymph node evaluation/axillary lymph node dissection with final surgical pathology data. Patients were classified into pathologic complete response (pCR) of the axilla group and non-pCR group based on surgical pathology. Breast MRI performed before NAC was used. Tumor was identified on first T1 postcontrast images underwent 3D segmentation. A total of 2811 volumetric slices of 127 tumors were evaluated. CNN consisted of 10 convolutional layers, 4 max-pooling layers. Dropout, augmentation and L2 regularization were implemented to prevent overfitting of data.ResultsOn final surgical pathology, 38.6% (49/127) of the patients achieved pCR of the axilla (group 1), and 61.4% (78/127) of the patients did not with residual metastasis detected (group 2). For predicting axillary pCR, our CNN algorithm achieved an overall accuracy of 83% (95% confidence interval [CI] ±u20095) with sensitivity of 93% (95% CI ±u20096) and specificity of 77% (95% CI ±u20094). Area under the ROC curve (0.93, 95% CI ±u20090.04).ConclusionsIt is feasible to use CNN architecture to predict post NAC axillary pCR. Larger data set will likely improve our prediction model.

The success of NRG-GBM-RPA: biomarker-based classification, where to next?

Glioblastoma (GBM) is an aggressive primary brain tumor in which outcomes are poor (1). Treatment for GBM had been limited until 2005 with the seminal study by Stupp and colleagues in which the addition of concurrent and adjuvant temozolomide (TMZ) to adjuvant radiotherapy improved median overall survival (mOS) by approximately 2.5 months (2). Since then, radiation therapy with TMZ has been the backbone for management of GBM in the postoperative setting. Initially developed in 1993, the recursive partitioning analysis (RPA) was created to prognosticate patients with high-grade gliomas (including anaplastic astrocytoma and GBM) (3). This classification was further modified and verified in GBM patients treated with radiation and TMZ (1,4).

Koebner phenomenon: Consideration when choosing fractionation for breast irradiation

A 62-year-old woman with a remote medical history of psoriasis initially presented with a palpable right breast mass. She underwent right breast ultrasound that revealed a hypoechoic mass at 10:30, 6 cm from the nipple, that measured 1.7 × 2.1 × 2.1 cm. Biopsy of the mass revealed invasive ductal carcinoma. Subsequent breast magnetic resonance imaging scans confirmed the right breast cancer, but also revealed a suspicious left breast region at 1:00. Biopsy of the left breast mass revealed a radial scar. The patient was evaluated by both breast and plastic surgery physicians and subsequently underwent right partial mastectomy and sentinel lymph node biopsy and excisional biopsy for the radial scar followed by bilateral oncoplastic breast reduction. Final pathology showed right breast multifocal invasive ductal carcinoma, grade 3, with no involved sentinel nodes, and left breast ductal carcinoma in situ. The patient’s postoperative course was complicated by bilateral seromas requiring drainage as well as bilateral breast cellulitis treated with antibiotics. She was evaluated by the radiation oncology department, and the decision was made to delay starting radiation to allow adequate wound healing. In the interim, she was started on Anastrazole 1 mg. The patient was assessed weekly, and eventually radiation was begun on the right breast, with the left side delayed to allow for further healing. The patient was treated in the prone position with hypofractionated whole breast radiation therapy (WBRT) of 42.56 Gy in 16 fractions with a 10 Gy boost to the right breast starting November 21. She completed treatment on December 21 without treatment breaks. During the second week of treatment, using daily Hydrophor and topical hydrocortisone as needed, the patient developed grade 1 erythema and pruritus of the right breast. After her leftsided seroma drainage resolved, she started adjuvant hypofractionated WBRT of 42.56 Gy in 16 fractions to the left breast on January 5, which she completed on January 27 without treatment breaks. During the second week of treatment, the patient developed grade 1 erythema of the left breast. Her right breast erythema improved with mild hyperpigmentation. The patient was seen for routine follow-up on March 1 approximately 1 month after completing her left breast radiation course. The patient noted that the erythema in her left breast was resolving (Fig 1a); however, over the course of the following few days, she noted a new rash on her right breast (Fig 2a) in the distribution of her radiation field (Fig 2b), along with similar rashes in her right inguinal region (Fig 1b) and her left wrist. The patient’s psoriasis had been inactive for more than 5 years. She was seen by her dermatologist, who suspected Koebner phenomenon. The patient underwent biopsy of the right inguinal rash; Conflicts of interest: None. * Corresponding author. Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032. E-mail address: dph2119@cumc.columbia.edu (D.P. Horowitz). 1 C.-C.W. and S.W. contributed equally to this work. Advances in Radiation Oncology (2018) 3, 108–110