Tracy Kelly

Neoadjuvant FOLFIRINOX for Borderline Resectable Pancreas Cancer: A New Treatment Paradigm?

BACKGROUND Borderline resectable pancreatic cancer is best treated by multimodality therapy. FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) tripled the response rate and significantly increased median survival for patients with advanced pancreatic cancer and shows promise for neoadjuvant use. Toxicity concerns prompted a careful analysis of our initial FOLFIRINOX experience. METHODS All patients diagnosed with borderline resectable, biopsy-proven pancreatic adenocarcinoma treated with neoadjuvant FOLFIRINOX between July 2010 and December 2012 were reviewed. Primary outcome was surgical resectability. Secondary outcomes were treatment-related toxicities and survival. RESULTS FOLFIRINOX followed by gemcitabine- or capecitabine-based chemoradiation was initiated in 18 patients. The most common grade 3 or 4 toxicities during chemotherapy were gastrointestinal, including nausea/emesis (n = 5), weight loss (n = 3) and diarrhea (n = 2), and hematologic (n = 2; neutropenia); five patients (36%) required a total of six admissions. Neoadjuvant therapy was completed in 15 of 18 patients (83%), and 12 (67%) underwent pancreatectomy (10 Whipple, 2 total pancreatectomy) including portal vein resection/reconstruction in 10 (83%). Disease progression precluded surgery in 6 of the 18 patients (33%). All 12 resected patients had negative (R0) margins. Only 2 of 12 (17%) were node positive (median node count: 26.5 [range: 15-39]). There were no in-hospital or 30-day mortalities and no clinical pancreatic leaks or reoperations. Of the 12 patients who completed all intended therapy, 7 (58.3%) are alive, including 5 who have no evidence of disease (median months from diagnosis: 22 months [range: 18-35 months). The six patients who did not complete all planned therapy are deceased (months from diagnosis: 6.9-17.5 months). CONCLUSION FOLFIRINOX followed by chemoradiation as neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma is safe, and our initial experience suggests favorable resection rates compared with previous reports in this high-risk patient population.

Cross-reactivity of food allergens in latex allergy.

Allergy resulting from exposure to latex proteins has been reported with increasing frequency in certain patient and occupational groups. Patients with latex allergy demonstrate cross-reactivity with some food allergens. Although amino acid homology of a few polypeptides from food and latex have been reported, no information is available comparing food and latex allergens. In the present study, we have obtained antibody from latex-sensitive patients by affinity absorption with various food and latex allergen extracts. The antibodies were then evaluated for reactivity with various antigens by ELISA. The results indicated that IgE cross-reactivity existed between different latex and food antigens. Hence, care should be exercised during evaluation of patients, as the clinical response may not be directed to the primary sensitizing antigen and may represent cross-reactivity of antigens.

Prone Whole-Breast Irradiation Using Three-Dimensional Conformal Radiotherapy in Women Undergoing Breast Conservation for Early Disease Yields High Rates of Excellent to Good Cosmetic Outcomes in Patients With Large and/or Pendulous Breasts

PURPOSE To report our institutions experience using prone positioning for three-dimensional conformal radiotherapy (3D-CRT) to deliver post-lumpectomy whole breast irradiation (WBI) in a cohort of women with large and/or pendulous breasts, to determine the rate of acute and late toxicities and, more specifically, cosmetic outcomes. We hypothesized that using 3D-CRT for WBI in the prone position would reduce or eliminate patient and breast size as negative prognostic indicators for toxicities associated with WBI. METHODS AND MATERIALS From 1998 to 2006, 110 cases were treated with prone WBI using 3D-CRT. The lumpectomy, breast target volumes, heart, and lung were contoured on all computed tomography scans. A dose of 45-50 Gy was prescribed to the breast volume using standard fractionation schemes. The planning goals were ≥95% of prescription to 95% of the breast volume, and 100% of boost dose to 95% of lumpectomy planning target volume. Toxicities and cosmesis were prospectively scored using the Common Terminology Criteria for Adverse Effects Version 3.0 and the Harvard Scale. The median follow-up was 40 months. RESULTS The median body mass index (BMI) was 33.6 kg/m(2), and median breast volume was 1396 cm(3). The worst toxicity encountered during radiation was Grade 3 dermatitis in 5% of our patient population. Moist desquamation occurred in 16% of patients, with only 2% of patients with moist desquamation outside the inframammary/axillary folds. Eleven percent of patients had Grade ≥2 late toxicities, including Grade 3 induration/fibrosis in 2%. Excellent to good cosmesis was achieved in 89%. Higher BMI was associated with moist desquamation and breast pain, but BMI and breast volume did not impact fibrosis or excellent to good cosmesis. CONCLUSION In patients with higher BMI and/or large-pendulous breasts, delivering prone WBI using 3D-CRT results in favorable toxicity profiles and high excellent to good cosmesis rates. Higher BMI was associated with moist desquamation, but prone positioning removed BMI and breast size as factors for poorer cosmetic outcomes. This series adds to the growing literature demonstrating that prone WBI may be advantageous in select patients.

Development of an online adaptive solution to account for inter- and intra-fractional variations

PURPOSE The current IGRT repositioning cannot fully account for the organ deformation and rotation. We introduce a comprehensive solution using gated IMRT with online adaptive replanning to manage both inter- and intra-fractional variations. METHODS AND MATERIALS The solution includes (1) generating respiration-gated IMRT plans based on 4DCT, (2) acquiring daily gated CT in treatment position prior to the treatment using a diagnostic-quality in-room CT (CTVision, Siemens) with the same gating window as that for the planning CT, (3) performing online repositioning or adaptive replanning based on the gated CT of the day, and (4) delivering the treatment with gating. The entire solution is demonstrated with RT data from 10 selected pancreatic cancer cases. The dosimetric impact of various advanced delivery technologies was investigated. RESULTS The online adaptive replanning based on the CT of the day combining with gating significantly improves normal tissue sparing during RT for pancreatic cancer. As the complexity of the delivery technology increases from no IGRT to with IGRT, gating and online adaptive replanning, the inter- and intra-fractional variations can be accounted for with increased adequacy. CONCLUSION The online adaptive replanning technique based on daily respiration-gated diagnostic-quality CT combined with gated delivery can effectively correct for inter- and intra-fraction variations during radiation therapy.

Neoadjuvant Chemoradiation with IMRT in Resectable and Borderline Resectable Pancreatic Cancer

PURPOSE Neoadjuvant chemoradiation is an alternative to the surgery-first approach for resectable pancreatic cancer (PDA) and represents the standard of care for borderline resectable (BLR). MATERIALS AND METHODS All patients with resectable and BLR PDA treated with neoadjuvant chemoradiation using IMRT between 1/2009 and 11/2011 were reviewed. Patients were treated to a customized CTV which included the primary mass and regional vessels. RESULTS Neoadjuvant chemoradiation was completed in 69 patients (39 BLR and 30 resectable). Induction chemotherapy was used in 32 (82%) of the 39 patients with BLR disease prior to chemoXRT. All resectable patients were treated with chemoXRT alone. Following neoadjuvant treatment, 48 (70%) of the 69 patients underwent successful pancreatic resection with 47 (98%) being margin negative (RO). In 30 of the BLR patients who had arterial abutment or SMV occlusion, 19 (63%) were surgically resected and all had RO resections. The cumulative incidence of local failure at 1 and 2 years was 2% (95% CI 0-6%) and 9% (95% CI 0.6-17%) respectively. The median overall survival for all patients, patients undergoing resection, and patients without resection were 20, 26 and 11 months respectively. Sixteen (23%) of the 69 patients are alive without disease with a median follow-up of 47 months (36-60). CONCLUSION Neoadjuvant chemoXRT can facilitate a margin negative resection in patients with localized PCa.

Long-term outcome from RTOG 9517: A phase I/II study of accelerated partial breast irradiation (APBI) with mulitcatheter brachytherapy (MCT) following lumpectomy for early-stage breast cancer.

147 Background: Comparison of APBI to whole breast irradiation post lumpectomy for breast conservation is ongoing in phase III trials. However, APBI has gained acceptance in clinical practice despite relatively limited long-term data. RTOG 9517 studied MCT, one of the earliest methods of APBI, and can uniquely provide long-term cancer outcomes. METHODS Eligibility was stage I/II unifocal breast cancer <3cm, invasive non-lobular histology without EIC, negative surgical margins, and 0-3 positive axillary nodes; no extracapsular extension. The target volume was the lumpectomy cavity plus a 2 cm radial and 1 cm ant/post margin. Low Dose Rate (LDR), 45 Gy in 3.5-5 day, or High Dose Rate (HDR) 34 Gy in 10 BID fractions over 5 days was delivered. A rapid dosimetry review was done to assure dose delivery per protocol. Systemic therapy was per physicians discretion. The primary endpoint was HDR and LDR MCT reproducibility. This analysis focuses on ipsilateral breast failure (IBF), contralateral breast cancer events (CBE), regional (RF) and distant failure (DF) (cumulative incidence) disease-free (DFS), relapse-free (RFS), and overall survival (OS), (Kaplan-Meier). RESULTS The median follow up is 12.1 years (yr). 100 patients were accrued from 1997-2000; 98 were evaluable; 65 HDR and 33 LDR MCT. Median age was 62; 88% had T1 tumors; 12% T2; 81% p N0, 19% pN1; 77% ER and/or PR +; 19% ER - and PR -; 33 % received adjuvant chemotherapy and 64% antiendocrine therapy. There have been 6 IBF for a 10 yr rate of 6.2%; 2 IBF were outside the APBI field. There were 5 total RF for a 10 yr rate of 5.2%, respectively. There have been 5 CBE for a 10 yr rate of 4.2%. Failure patterns were: 4 isolated IBF, 1 isolated RF, 8 DF only, 1 IBF+RF, 1 IBF+RF+DF, 1 RF+CBE, 1 RF+DF, 3 CBE, and 1 CBE+DF (21 total failures). Eleven patients have developed DF; 8 have died of breast cancer, 22 have died from other causes. The 10 yr DFS, RFS and OS are 69.8%, 71.9%, and 78.0%, respectively. CONCLUSIONS This multi-institutional phase II trial studying MCT-APBI continues to report durable local regional cancer control rates with long term follow-up. Supported by NCI U10 grants CA21661 and CA37422.

Adaptive Replanning to Account for Lumpectomy Cavity Change in Sequential Boost After Whole-Breast Irradiation

PURPOSE To evaluate the efficiency of standard image-guided radiation therapy (IGRT) to account for lumpectomy cavity (LC) variation during whole-breast irradiation (WBI) and propose an adaptive strategy to improve dosimetry if IGRT fails to address the interfraction LC variations. METHODS AND MATERIALS Daily diagnostic-quality CT data acquired during IGRT in the boost stage using an in-room CT for 19 breast cancer patients treated with sequential boost after WBI in the prone position were retrospectively analyzed. Contours of the LC, treated breast, ipsilateral lung, and heart were generated by populating contours from planning CTs to boost fraction CTs using an auto-segmentation tool with manual editing. Three plans were generated on each fraction CT: (1) a repositioning plan by applying the original boost plan with the shift determined by IGRT; (2) an adaptive plan by modifying the original plan according to a fraction CT; and (3) a reoptimization plan by a full-scale optimization. RESULTS Significant variations were observed in LC. The change in LC volume at the first boost fraction ranged from a 70% decrease to a 50% increase of that on the planning CT. The adaptive and reoptimization plans were comparable. Compared with the repositioning plans, the adaptive plans led to an improvement in target coverage for an increased LC case (1 of 19, 7.5% increase in planning target volume evaluation volume V95%), and breast tissue sparing for an LC decrease larger than 35% (3 of 19, 7.5% decrease in breast evaluation volume V50%; P=.008). CONCLUSION Significant changes in LC shape and volume at the time of boost that deviate from the original plan for WBI with sequential boost can be addressed by adaptive replanning at the first boost fraction.

Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes.

Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x‐rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long‐term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.

Abstract P1-15-17: Sustained acceptable cosmetic outcomes and local control following accelerated partial breast irradiation using CT-guided IMRT in the prone position: Results from a phase I/II feasibility study

Objective/Purpose External beam accelerated partial breast irradiation (EB-aPBI) can have potential challenges in daily reproducibility, although it has broader potential use than aPBI using brachytherapy. Image-guide radiotherapy (IGRT) can improve daily reproducibility and allow smaller treatment margins. Our institution utilized IG-IMRT to administer EB-aPBI in the prone position in a Phase I/II study to increase dose homogeneity, conformality, normal tissue avoidance, and reliable targeting. Our preliminary results and toxicity were promising. Here we report final physician- and patient-reported cosmetic outcomes from this prospective trial. Materials and Methods Women with node-negative invasive breast cancer or DCIS, tumors less than 3.0 cm, a negative sentinel lymph node biopsy, and surgical clips demarcating the lumpectomy cavity underwent prone EB-aPBI using IG-IMRT on an IRB-approved phase I/II study. The lumpectomy PTV represented a 2.0 cm lumpectomy cavity expansion. 38.5 Gy was delivered in 10 fractions over 5 days, such that 95% of the prescribed dose covered greater than 99% of the PTV. Dose constraints for the whole breast, lungs and heart were met. Results Twenty patients were enrolled, with a median patient age of 61.5 and a mean tumor size of 1.0 cm. 35% of patients had DCIS. At a median follow-up of 18.9 months, 40% and 10% of patients had G1 and G2 fibrosis, respectively, and 95% of patients had good to excellent physician-assessed cosmesis. At a median follow-up of 60.0 months (range 54-79 months), physician-assessed cosmetic outcome was good to excellent in 80%, with 30% and 20% of patients experiencing G1 and G2 fibrosis. Patient-reported outcomes at one year yielded 90% of patients with good to excellent cosmetic outcomes. At 3 years, 75% of patients reported good to excellent cosmesis. Eighty-eight percent of patients were completely satisfied with the treatment and results, and 94% of patients would choose aPBI again. With one local recurrence, the actuarial five year rate of local control was 95%. Conclusions These data demonstrate that EB-aPBI in the prone position using IG-IMRT continues to yield acceptable cosmetic outcomes at longer term follow-up, and a very high percentage of patients would choose this treatment again. (Supported by Komen Grant: BCTR0504070). Citation Format: Carmen Bergom, Phillip Prior, Kristofer Kainz, Natalya V Morrow, Ergun E Ahunbay, Alonzo Walker, X Allen Li, Tracy Kelly, Adam D Currey, Julia White. Sustained acceptable cosmetic outcomes and local control following accelerated partial breast irradiation using CT-guided IMRT in the prone position: Results from a phase I/II feasibility study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-17.