J.L. Oh

External-Beam Accelerated Partial Breast Irradiation Using Multiple Proton Beam Configurations

PURPOSE To explore multiple proton beam configurations for optimizing dosimetry and minimizing uncertainties for accelerated partial breast irradiation (APBI) and to compare the dosimetry of proton with that of photon radiotherapy for treatment of the same clinical volumes. METHODS AND MATERIALS Proton treatment plans were created for 11 sequential patients treated with three-dimensional radiotherapy (3DCRT) photon APBI using passive scattering proton beams (PSPB) and were compared with clinically treated 3DCRT photon plans. Monte Carlo calculations were used to verify the accuracy of the proton dose calculation from the treatment planning system. The impact of range, motion, and setup uncertainty was evaluated with tangential vs. en face beams. RESULTS Compared with 3DCRT photons, the absolute reduction of the mean of V100 (the volume receiving 100% of prescription dose), V90, V75, V50, and V20 for normal breast using protons are 3.4%, 8.6%, 11.8%, 17.9%, and 23.6%, respectively. For breast skin, with the similar V90 as 3DCRT photons, the proton plan significantly reduced V75, V50, V30, and V10. The proton plan also significantly reduced the dose to the lung and heart. Dose distributions from Monte Carlo simulations demonstrated minimal deviation from the treatment planning system. The tangential beam configuration showed significantly less dose fluctuation in the chest wall region but was more vulnerable to respiratory motion than that for the en face beams. Worst-case analysis demonstrated the robustness of designed proton beams with range and patient setup uncertainties. CONCLUSIONS APBI using multiple proton beams spares significantly more normal tissue, including nontarget breast and breast skin, than 3DCRT using photons. It is robust, considering the range and patient setup uncertainties.

Mucinous Breast Carcinoma: Occult Multifocality/Multicentricity in a Favorable Disease.

Purpose: Mucinous carcinoma is a distinctive tumor that reportedly has a very favorable prognosis. Accordingly, investigators have recommended that patients be treated with minimal effective therapy rather than maximum tolerated treatment. However, previous reports have been limited by small sample sizes and very short follow-up intervals. We have previously reported outcomes for a mature data set with long term follow-up and now perform the current analysis to emphasize comprehensive multidisciplinary management in an era of minimal effective therapy for so-called favorable disease.Methods and Materials: We retrospectively reviewed charts for 264 patients with a pure mucinous carcinoma diagnosis at our institution from 1965-2005. Multidisciplinary management is emphasized for all patients at our institution including this patient cohort. All pathology was centrally reviewed. Overall survival, DM-free survival, and local-regional control were compared using Kaplan Meier method and log rank statistics.Results: Median age was 57 years (range 25-89). Median follow-up was 168 months. 86% of patients were stage T2 or less. Patients who were lymph node negative compared with 1-3 LN+, or 4 or more LN+ were 80%, 15%, and 5% respectively. 44% received BCT while the remainder underwent mastectomy. 51% of all patients received XRT. No patient in this cohort received partial breast irradiation. 10% of patients had an initial multicentric/multifocal presentation. However, a detailed pathology review revealed a 38% multifocal/multicentric disease rate after surgical resection. The occult tumors were not initially detected by mammography or ultrasonography.5, 10, and 15 year OS, DMFS, and LRC rates for all patients were: 95%/88%/83%; 97%/95%/92%; and 97%/94%/85% respectively. There was no statistically significant difference in OS, DMFS, or LRC based upon surgical management by mastectomy in comparison with BCT. Likewise, there was no statistically significant improvement in OS or DMFS with utilization of whole breast XRT. There was, however, a trend for improved LRC in patients who received XRT (p=0.06) in comparison with patients who underwent mastectomy or BCT without XRT.Conclusions: This large series of patients diagnosed with pure mucinous breast carcinoma demonstrates potentially favorable prognosis. However, this is the first known report of an association with significant occult multicentricity/multifocality. In an era of minimal effective cancer therapy which includes no additional treatment post resection in favorable histology, and partial breast XRT in favorable histology, multidisciplinary management inclusive of pathology and diagnostic imaging is recommended. Current treatment guidelines should reflect that before omitting whole breast XRT, patients should have pathologic and radiologic intraoperative correlation and MRI should be a consideration in efforts to identify potential occult disease. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4117.

Local-regional recurrence with and without radiation after neoadjuvant chemotherapy and mastectomy for T3N0 breast cancer patients.

Abstract #74 Purpose: The goal of this study was to compare the local-regional recurrence (LRR) risk in patients with clinical T3N0 breast cancer who were treated with neoadjuvant chemotherapy (NeoChemo) and mastectomy (Mastx) according to the use of adjuvant radiation (RT).
 Methods: Clinicopathologic data from 164 patients with clinical T3N0 breast cancer who received NeoChemo and Mastx from 1985 to 2004 were retrospectively reviewed. In this cohort, 121 (74%) patients received adjuvant radiation (RT) while 43 (26%) patients did not. The median number of axillary lymph nodes (LN) dissected was 15. After NeoChemo, 54% of patients (n=89) had no pathologically involved lymph nodes at the time of surgery (ypLN-) while 46% (n=75) had at least 1 lymph node pathologically positive (ypLN+). Actuarial rates were calculated using Kaplan-Meier analysis and compared using log-rank test. Cox proportional hazards models were fit to determine the association of RT with the risk of LRR after adjustment for other patient and disease characteristics.
 Results: At a median follow-up of 77 months, 17 of the 164 patients had a LRR. For all patients, the 5-year local-regional control rates (5-yr LRC) were 90%. The 5-yr LRC for those who received RT (n=121) was 95% and for those who did not received RT (n=43) was 76% (p = 0.002), with a higher proportion of the patients who received RT having pathologically involved LN (+RT 53% vs –RT 23%, p=0.002).
 Among the entire cohort, the 5-yr LRC was 85% for patients with ypLN+ disease and 94% for patients with ypLN- disease (p=0.093). In patients with ypLN+, the 5-yr LRC with no RT (n=11) was 47% and with RT (n=64) was 92% (p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 74.

Clinical Data Do Not Support the Hypothesis That Irradiation Promotes Biologically Aggressive Local Recurrences through Stromal Activation.

Objective: Recent data in select pre-clinical models suggest that radiation can activate normal stroma to promote tumor metastases and aggressiveness. We hypothesized that if these were occurring clinically, there would be a lower survival after locoregional recurrence (LRR) in patients after post-mastectomy radiation therapy (PMRT) compared to mastectomy (Mx) alone. This study used two independent datasets to compare survival after LRR in women treated with versus without PMRT.Methods: Data from 229 of 1,505 patients who experienced LRR after treatment on sequential non-randomized institutional prospective trials at the MD Anderson Cancer Center (MDA) and 66 of 318 patients enrolled in the British Columbia (BC) PMRT randomized trial who experienced LRR were analyzed. All patients underwent Mx and level I/II axillary dissection. In both data sets analysis was based on treatment received. Patients from MDA received doxorubicin based chemotherapy +/- PMRT, with 45 LRR after PMRT and 184 LRR after Mx alone). Patients treated on the BC trial received CMF chemotherapy +/- PMRT, with LRR in 14/160 after PMRT versus 52/158 after Mx alone. Survival was calculated from time of LRR to death using Kaplan-Meier and log rank statistics.Results:MDA Data: Median follow up of living patients was 192 months. Analyzing data from all patients with LRR regardless of distant metastasis (DM), patients with LRR after PMRT were younger (47 vs. 51 y, p = 0.033) and had shorter time to first LRR (40mo vs. 51 mo, p = 0.018). 5-yr/10-yr OS were 31%/16% without PMRT and 20%/7% after PMRT (p = 0.008). However, PMRT-treated patients had increased risk factors for DM (advanced T and N stage) and more PMRT-treated patients developed DM prior to LRR (58% vs. 36% p = 0.009). Analyzing only patients without DM there was no difference in OS between groups (p = 0.67), and a separate analysis of all patients who developed metastatic disease (N = 385 no PMRT, 233 after PMRT) revealed no difference in 5 or 10-yr OS after DR (15%/4% without PMRT vs. 13%/6% after PMRT, p = 0.5).BC Data: Median follow up of living patients was 235 months. The distributions of age, T stage, N stage, grade, LVI, ER status, excised nodes and nodal ratio were similar between patients with LRR after Mx alone vs. Mx plus PMRT. (all p > 0.05). The mean time to first LRR was 39 mo in patients treated with Mx alone and 57 mo in patients treated with PMRT, p= 0.27). The rate of DM was similar in patients with LRR after Mx with vs without PMRT (93% vs. 96%, p=0.60). Distant relapse free survival after LRR was similar in Mx alone vs. PMRT-treated patients (log rank p=0.75). Overall survival was also similar in the two groups (5-yr/10-yr OS 21%/8% without PMRT vs. 23%/12% with PMRT, log rank p=0.93).Conclusions: Decades of randomized data have demonstrated that PMRT reduces LRR and improves overall survival. In the non-randomized dataset, removing the competing risk of DM which is higher in patients selected for PMRT by studying patients with isolated LRR, we find no difference in survival after LRR in the PMRT setting. Analysis of the randomized PMRT trial dataset confirmed the finding of similar survival among women with LRR irrespective of PMRT use. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4101.

Male breast cancer outcomes: validation and modification of a guideline.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #4131 Purpose : Previously, we have proposed that male patients be staged, treated, and evaluated for outcomes similar to women with breast cancer. This study examines the outcomes of our recommended guideline. Methods and Materials : 262 patients were registered at our institution between 1944 and 2008 and were reviewed per an IRB approved protocol. Patients having metastatic, recurrent, bilateral, and inflammatory disease were excluded. Radiology and pathology were reviewed. Surgical techniques, systemic therapy utilization, and XRT use were analyzed. Descriptive, Kaplan-Meier, and log-rank statistics were generated. Results : 233 patients were evaluable. Median age was 60 years. Mean follow-up was 95 months. Laterality was equally distributed. 60% had a positive family history. 45% were T1. 52% were clinically node negative. Only 29% underwent any staging-related imaging. Over 80% of the patients whose hormonal status was known were ER +; fewer than 7% of the patients were margin positive. 90% of patients had mastectomy while 7% were managed by conservation. 90% of patients whose systemic therapy recommendation was known received tamoxifen. 65% received no chemotherapy while 23% received doxorubicin -based, 5% received taxanes, and 5% received novel systemic regimens. 39% received radiation therapy and the median dose was 55Gy. The 5 and 10 year OS, DMFS, and LRC for the entire cohort was 72%/47%, 68%/49%, and 87%/81%. OS was significantly improved by smaller tumor size, decreased number of positive nodes, and receipt of adjuvant hormonal therapy ( all p 0.15). Interestingly, there was no significant OS benefit with the utilization of chemotherapy (p=.60) although patients receiving novel regimens or regimens with doxorubicin and taxanes had better OS (10% of all patients and NSS). Decreased OS was noted in patients treated with conservation approach as compared to mastectomy (p 0.15)); and decreased with use of conservation (p=0.04). DMFS : improved with smaller tumor size, less LN+, and adjuvant hormonal therapy (all p 0.2). Conclusions : Our study confirms our recommended guidelines for MBC;however, the presence of skin and nipple involvement does not appear to predict outcome. Conservation should be utilized in selected patients and XRT emphasized. Chemotherapy was utilized in worse prognosis patients yet OS, and DMFS was equivalent to favorable groups. Modifications should be made to update guidelines for future studies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4131.