Lonika Majithia

Defining the role of adjuvant therapy: cholangiocarcinoma and gall bladder cancer.

Biliary tract cancers are a rare subgroup of malignancies that include gall bladder carcinoma and cholangiocarcinoma. They generally carry a poor prognosis based on the advanced nature of disease at presentation and overall treatment refractoriness. Surgical resection remains the optimal treatment for long-term survival, with consideration of neoadjuvant or adjuvant therapies. In this review, we summarize the role of adjuvant treatments including radiation therapy, chemotherapy, and concurrent chemoradiation with the existing clinical evidence for each treatment decision. Given the rarity of these tumors, the evidence provided is based largely on retrospective studies, Surveillance, Epidemiological, and End Results (SEER) database inquiries, single- or multi-institutional prospective studies, and a meta-analysis of adjuvant therapy studies. Currently, there is no adjuvant therapy that has been agreed upon as a standard of care. Results from prospective, multi-institutional phase II and III trials are awaited, along with advances in molecular targeted therapies and radiation techniques, which will better define treatment standards and improve outcomes in this group of diseases.

SU‐E‐T‐564: Validation of Photon Dose Calculation Using Mobius3D System Compared to AAA and Acuros XB Systems

PURPOSE To study the Collapsed Cone Convolution/Superposition algorithm in Mobius 3D system for dose calculations in comparison to Acuros XB and AAA dose calculation algorithms in Eclipse treatment planning system. METHODS Dose modeling or correction at density heterogeneity (lung/tissue or bone/tissue interfaces) remains an area of maximum discord amongst treatment planning systems. Thus, four phantoms were constructed and CT scanned with both horizontal and vertical density heterogeneity interfaces. Treatment plans were created with varying field sizes (3×3 cm2 , 5×5 cm2 , and 10×1 0 cm2 ) and energies (6FFF, 6MV, and 15 MV). All plans were created in Eclipse TPS with one single AP field, 100 cm SSD, 1 mm grid size for improved resolution, and 200 MU. Plans were calculated with AAA and Acuros XB algorithms and exported to Mobius3D for recalculation and comparison. Percent depth dose (PDD) and horizontal profiles at multiple depths through density heterogeneity interfaces were compared and analyzed. RPC Lung phantom was also used for complex plan (3DCRT and IMRT) dose comparisons. RESULTS Examination of PDD and horizontal dose profiles were reported graphically and numerically. Highest conformality was noted between AcurosXB and Mobius3D in homogenous sites. CCC in Mobius3D generally matches closer with AcurosXB, especially for large field sizes, compared to AAA. In PDDs, Mobius3D tends to under-predict dose compared to AcurosXB at the tissue-to-water interface up to 3%, while over-predicting dose in and beyond the lung-to-tissue interface compared to AcurosXB up to 7%. In 10×10 profiles with vertical heterogeneity interface, Mobius3D agrees with AcurosXB within 3%/3mm for 6MV and 15MV, but higher difference was seen for 6X-FFF. CONCLUSION The recently released Mobius3D program offers physicist and physician ease in evaluation, rapid plan review, and dose second check to TPS calculations. Future research directions include confirmatory clinical dose calculations and additional evaluation with patient geometry.

Treating Cutaneous T-Cell Lymphoma with Highly Irregular Surfaces with Photon Irradiation Using Rice as Tissue Compensator

Purpose: Cutaneous T-cell lymphoma (CTCL) is known to have an excellent response to radiotherapy, an important treatment modality for this disease. In patients with extremity and digit involvement, the irregular surface and depth variations create difficulty in delivering a homogenous dose using electrons. We sought to evaluate photon irradiation with rice packing as tissue equivalence and determine clinical tolerance and response. Materials and methods: Three consecutive CTCL patients with extensive lower extremity involvement including the digits were treated using external beam photon therapy with rice packing for tissue compensation. The entire foot was treated to 30–40 Gy in 2–3 Gy per fraction using 6 MV photons prescribed to the mid-plane of an indexed box filled with rice in which the foot was placed. Treatment tolerance and response were monitored with clinical evaluation. Results: All patients tolerated the treatment without treatment breaks. Toxicities included grade 3 erythema and desquamation with resolution within 4 weeks. No late toxicities were observed. All patients had a partial response by 4 weeks after therapy with two patients achieving a complete response. Patients reported improved functionality after treatment. No local recurrence has been observed. Conclusion: Tissue compensation with rice packing offers a convenient, inexpensive, and reproducible method for the treatment of CTCL with highly irregular surfaces.

Use of Neuroimaging for Radiation Therapy Planning

Intracranial tumors, both primary and metastatic, have distinct anatomic and neuroimaging features. Radiotherapy is often used in the management of intracranial tumors. Various techniques used in radiotherapy include external beam radiotherapy and stereotactic radiotherapy. This chapter discusses the use of neuroimaging in tumor delineation and radiation planning and delivery. Evaluation of immobilization, target volumes, normal tissue volumes, plan review, and quality assurance is required to safely deliver radiotherapy. The practical review of radiotherapy in high-grade glioma is used to demonstrate these facets of patient care. Neuroimaging and clinical evaluation are used to evaluate for disease recurrence following treatment completion. On standard magnetic resonance imaging, it may be difficult to differentiate between pseudo-progression, true disease progression, and radiation necrosis. A multitude of imaging techniques are now available to assist in making this distinction. The progress in neuroimaging has improved radiation planning and delivery and will continue to do so in the future.

Abstract P3-12-01: Locoregional failure rates do not vary by breast cancer subtype after mastectomy in a modern cohort of patients with T1-2 tumors with 1-3 pathologically involved lymph nodes

Purpose/Objective(s): A recent meta-analysis of 22 randomized trials accrued between 1964-86 demonstrated significantly higher rates of locoregional failure (LRF), total failure (TF) and breast-cancer mortality in women with 1-3 positive (+) axillary lymph nodes (ALN) who did not receive radiotherapy after mastectomy (mast.). Given the improvements in diagnostic and therapeutic approaches, the challenge today is whether breast cancer patients with T1-T2 tumors with 1-3+ ALN have similar substantial risk that routinely warrants the delivery of post mastectomy radiotherapy (PMRT). We further set out to explore whether the risk of failure varies by breast cancer subtype. Materials/Methods: We reviewed patients with pathologic T1-2N1 breast cancer treated with initial mast. and adjuvant systemic therapy (ST) from 2000-2013. The primary endpoint was LRF, defined as a recurrence in either the ipsilateral chestwall or regional lympatics (axillary, internal mammary, or supraclavicular nodes). Secondary endpoints include rates of TF (LRF or distant metastases), disease-free survival (DFS, failure or death), and overall survival (OS). Patients were classified into 3 basic subtypes: hormone receptor positive/HER2 negative (HR+), HER2 positive (HER2+), and triple negative (TN). Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used to compare survival between groups. Results : We identified 550 eligible patients from our prospectively maintained cancer registry. Median follow-up was 5 years. Baseline characteristics included median age 53 yrs, 61% pathologic T2, 39% grade 3, 48% with lymphovascular invasion. Subtypes included 72% HR+ (n=393), 16% HER2+ (n=89), 12% TN (n=66) and 0.4% unknown (n=2). Treatment included chemotherapy in 78% (n=428), PMRT in 15% (n=82), and anti-endocrine therapy in 70% (n=385). A median of 18 ALN (range, 1-68) were removed, 10% (N=55) had sentinel-lymph node biopsy only, and 17%(N=95) had micrometastases (N1mic) only. A total of 296 pts had 1+ node, 165 pts 2+ nodes and 89 pts 3+ nodes. The 5 yr LRF rate for the entire cohort was 3.9% and patients with 1+, 2+, and 3+ nodes had 5 yr LRF of 2.6%, 4.7% and 6.4%, respectively (p=0.79). The 5 yr LRF for HR+, HER2+ and TN was 3.9%, 1.5%, and 6.6%, respectively (p=0.39). When stratified by 1+, 2+ or 3+ nodes, the 5 yr LRF for HR+ vs. HER2+ vs. TN were 2.4%, 6.8%, and 0% vs. 5.8%, 15.4%, and 0% vs. 5.7%, 0%, and 4.8%, p=0.43. The 5 yr TF, DFS, and OS rates for HR+, HER2+ and TN were 90.5% vs. 88.5%. vs. 83.6% (p=0.76); 84.9% vs. 82.6% vs. 79.2% (p=0.85); and 91.4% vs. 86.2% vs. 81.3% (p=0.83). Conclusions : In a cohort of patients with T1-2N1 breast cancer treated with modern therapy, we found low rates of LRF which did not vary amongst HR+, HER2+ and TN patients. In particular, HR+ patients with 1+ LN had extremely low rates of LRF Given these low recurrence rates, caution should be given in routinely recommending PMRT for every woman with 1-3+ ALN after mast. and adjuvant ST. Citation Format: Bazan JG, Majithia L, Quick AM, Terando AM, Agnese D, Mrozek E, Farrar W, White JR. Locoregional failure rates do not vary by breast cancer subtype after mastectomy in a modern cohort of patients with T1-2 tumors with 1-3 pathologically involved lymph nodes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-01.

Rates of unacceptable variation (UV) of normal tissue constraints in patients undergoing chest wall/breast and regional nodal irradiation (RNI) in a routine clinical practice.

67 Background: TheNSABP B51/RTOG 1304 clinical trial defines dose-volume constraints for targets/normal tissue receiving RNI. We sought to evaluate UV rate in normal tissue based on the NSABP B51/RTOG 1304 protocol in patients receiving chestwall/breast (CW/B) and RNI in daily practice. METHODS Treatment records of CW/B+RNI patients from 2/2012-5/2015 were studied for: CW or B radiotherapy (RT), RT type (intensity modulated [IMRT] or 3D conformal [3DCRT]), internal mammary node (IMN) inclusion, primary site boost, and nodal boost. No case is enrolled on B51/1304. Dose volume histogram (DVH) was analyzed for the rate of ≥ 1 UV for the following normal tissue constraints: Heart mean dose ≤ 5 Gy; ipsilateral lung (IL): V20 ≤ 35%, V10 ≤ 60%, V5 ≤ 70%; contralateral lung (CL) V5 ≤ 15%; contralateral breast (CB) V4.1 ≤ 5%. Logistic regression is used to test the association between UV and key variables. RESULTS 203 consecutive cases received CW/B+RNI (105 left, 98 right). RT was to CW in 170 (84%), B in 33 (16%), primary site boost 133 (66%), and IMN 170 (84%). 38 (19%) received IMRT and 14 (6.9%) had a nodal boost. 46 patients (22.6%) had ≥ 1 UV. 19 patients (9.4%) had ≥ 2 UV, all in IMRT patients. 2 patients (1.0%) had a heart UV at 5.2 Gy and 5.6 Gy. The most common UV was CB (n = 32, 15.7%) and IL V5 (n = 22, 10.8%). Higher UV rates are associated with use of IMRT (vs. 3DCRT): 86.8% vs. 7.9%, OR = 77.2 (95% CI 25.7-231.4, p < 0.0001); IMN irradiation: OR = 11.5 (95% CI 1.5-86.8, p = 0.02); and use of nodal boost: OR = 7.4 (95% CI 2.3-23.4, p = 0.001). The most common UVs in IMRT cases are CB (n = 27, 71%), IL V5 (n = 19, 50%), CL V5 (n = 14, 37%) and for 3DCRT are IL V20 (n = 5, 3%), CB (n = 5, 3%) and IL V5 (n = 3, 1.8%). On multivariate analysis, use of IMRT (OR = 64.7, 95% CI 20.8-201.5, p < 0.001) and use of nodal boost (OR = 5.5, 95% CI 1.1-27.1, p = 0.04) but not IMN irradiation (OR = 2.7, 95% CI 0.3-22.0, p = 0.35) were independently associated with higher UV rate. CONCLUSIONS The rate of UV per B51/1304 criteria with 3DCRT in routine clinical practice is low (7.9%). Women treated with IMRT had a significantly higher overall UV rate and clinicians should be aware of this as they initiate treatment planning for RNI.

Locoregional failure rates after mastectomy for breast cancer patients with T1-2 tumors and axillary nodal microscopic metastases.

64 Background: The indications for postmastectomy radiotherapy (PMRT) are expanding to include patients 1-3 axillary nodal metastases (ALN). Improvements in diagnostic evaluation have led to increasing numbers of breast cancer (BC) patients who are found to have microscopic nodal metastases (N1mic). The challenge today is whether these BC patients have risk that warrants the routine delivery of PMRT. METHODS We reviewed patients with pathologic T1-2N1 BC treated with initial mastectomy (mast) and adjuvant systemic therapy (ST) from 2000-2013. The primary endpoint was locoregional failure (LRF), defined as a recurrence in either the ipsilateral chestwall or regional lymphatics (axillary, internal mammary, or supraclavicular). Secondary endpoints were disease-free survival (DFS, failure or death) and overall survival (OS). The log-rank test was used to compare survival between groups. RESULTS We identified 550 eligible patients from our prospectively maintained cancer registry with 5 year median follow-up. 95 patients (17%) had N1mic disease. Baseline characteristics include: median age 53 yrs, 61% pathologic T2, 39% grade 3, 72% hormone receptor positive, 16% HER2+, 12% triple-negative. Treatment included chemotherapy in 78% (n = 428), PMRT in 15% (n = 82), and anti-endocrine therapy in 70% (n = 385). A median of 18 ALN (range, 1-68) were removed. Among the patients with N1mic disease, 81 had 1+ node, 13 had 2+ nodes, and 1 had 3+ nodes. The 5 yr LRF was 0% for patients with N1mic disease vs. 4.6% in those macro metastases (p = 0.84). The 5 yr LRF rate for the entire cohort was 3.9%; patients with 1+, 2+, and 3+ nodes had 5 yr LRF of 2.6%, 4.7% and 6.4%, respectively (p = 0.79). Patients with N1mic disease had a trend towards improved DFS (91.6% vs. 82.3%, p = 0.07) and significantly improved OS (96.9% vs. 87.6%, p = 0.03) compared to patients with macrometastases. CONCLUSIONS In a cohort of patients with T1-2,N1 BC treated with modern therapy, we found overall low rates of LRF. Patients with N1mic disease had no LRF events and improved OS compared to patients with macrometastases. These findings support that PMRT should not be routinely recommended for N1mic BC patients with T1-2 tumors.