Outcomes and toxicities after proton partial breast radiotherapy for early stage, hormone receptor positive breast cancer: 3-Year results of a phase II multi-center trial.

Purpose: Proton therapy (PT) for partial breast irradiation (PBI) in early-stage breast cancer can decrease morbidity versus photon PBI with superior organs-at-risk sparing. We report 3-year outcomes of the first prospective, multicenter, phase II trial of proton PBI. Methods and Materials: This Proton Collaborative Group phase II trial (PCG BRE007-12) recruited women ≥ 50 years with node-negative, estrogen receptor (ER)-positive, ≤3cm, invasive ductal carcinoma (IDC) or ductal carcinoma in situ undergoing breast conserving surgery followed by proton PBI (40 Gy(RBE), 10 daily fractions). Primary endpoint was freedom from ipsilateral breast cancer recurrence. Adverse events were prospectively graded using CTCAEv4.0. Breast Cancer Treatment Outcome Scale (BCTOS) assessed patient-reported quality of life (PRQOL). Results: Thirty-eight evaluable patients enrolled between 2/2013-11/2016. Median age was 67 years (range 50-79); 55 % had left-sided disease, and median tumor size was 0.9 cm. Treatment was delivered in ≥ 2 fields predominantly with uniform scanning PT (n = 37). At 35-month median follow-up (12-62), all patients were alive, and none had local, regional or distant disease progression. One patient developed an ER-negative contralateral IDC. Seven grade 2 adverse events occurred; no radiotherapy-related grade ≥ 3 toxicities occurred. Changes in BCTOS subdomain mean scores were maximum 0.36, indicating no meaningful change in PRQOL. Median heart volume receiving 5 Gy (V5Gy), lung V20Gy, and lung V10Gy were 0 %, 0 % and 0.19 %, respectively. Conclusion: At 3 years, proton PBI provided 100 % cancer control for early-stage, ER-positive breast cancer. Toxicities are minimal, and PRQOL remains acceptable with continued follow-up. These findings support PT as a safe and effective PBI delivery option.

The impact of heterogeneity correction on dosimetric parameters that predict for radiation pneumonitis.

PURPOSE: To determine if heterogeneity correction significantly affects commonly measured dosimetric parameters predicting pulmonary toxicity in patients receiving radiation for lung cancer. METHODS AND MATERIALS: Sixty-eight patients treated for lung cancer were evaluated. The conformal treatment technique mostly employed anteroposterior/posterior-anterior fields and off-cord obliques. The percent total lung volume receiving 20 Gy or higher (V20) and mean lung dose (MLD) were correlated with the incidence of radiation pneumonitis. Parameters from both heterogeneity-corrected and heterogeneity-uncorrected plans were used to assess this risk. RESULTS: Univariate analysis revealed a significant correlation between the development of radiation pneumonitis and both V20 and MLD. A best-fit line to a plot of V20 from the homogeneous plan against the corresponding V20 heterogeneous value produced a slope of 1.00 and zero offset, indicating no difference between the two parameters. For MLD, a similarly significant correlation is seen between the heterogeneous and homogeneous parameters, indicating a 4% difference when correcting for heterogeneity. A significant correlation was also observed between the MLD and V20 parameters (p < 0.0001). CONCLUSIONS: A high degree of correlation exists between heterogeneity-corrected and heterogeneity-uncorrected dosimetric parameters for lung and the risk of developing pneumonitis. Either V20 or MLD predicts the pneumonitis risk with similar effect.

Inflammatory breast carcinoma: outcomes with trimodality therapy for nonmetastatic disease.

BACKGROUND: The objectives of this study were to summarize a single-institution experience in treating patients with inflammatory breast carcinoma (IBC) using trimodality therapy and to identify prognostic factors for outcome. METHODS: Sixty-one women underwent radiation therapy with curative intent for IBC between 1982 and 2001. All but five women received trimodality therapy. Neoadjuvant chemotherapy was given to the majority of women (n = 43 patients), although some received "up-front" surgery as first therapy (n = 18 patients). RESULTS: With a median potential observation time after diagnosis of 14 years, freedom from locoregional disease progression was 78%, freedom from distant metastasis was 45%, and the cause-specific survival rate was 47% at 5 years. Approximately 40% of the 56 patients who received trimodality therapy remained free of disease. Multivariate analysis demonstrated three factors that were found to be associated significantly with improved cause-specific survival: pathologic tumor size < 4 cm (P = 0.0001), up-front surgery (P = 0.0078), and local disease control (P = 0.0003). Factors that were found to be associated with better freedom from locoregional disease progression were pathologic tumor size (< 4 cm; P = 0.0157), age (> 55 years; P = 0.0596), and radiation dose (> or = 60 grays [Gy]; P = 0.0621). CONCLUSIONS: IBC is an aggressive disease that is treated effectively in select patients by multimodality therapy. Patient outcomes may be improved with therapies that result in better local and systemic control. Further studies are warranted to address the optimal sequence of trimodality therapy and the optimal administration of each agent.

Should decisions on internal mammary lymph node irradiation be based on current lymphoscintigraphy techniques for sentinel lymph node identification?

BACKGROUND: Treatment of internal mammary lymph node (IMN) metastases remains controversial because of the difficulty in predicting involvement, potential treatment-related morbidity, and questionable efficacy. Lymphoscintigraphy with sentinel lymph node biopsy offers a means to identify occult involvement of IMN, allowing appropriate patient selection for IMN treatment. METHODS: The authors retrospectively reviewed 262 lymphoscintigraphies (LS) of 248 patients treated at the University of Florida (Gainesville, FL) between 1998 and 2002. Tumor characteristics were assessed for their value in predicting IMN drainage and their association with IMN radiation. RESULTS: Lymph flow to the IMN was documented with LS in 23 of 262 tumor specimens (9%). Flow to the IMN was not correlated with any of the five factors: tumor location, tumor size, lymphovascular invasion, pathologic lymph node status, and laterality of the involved breast (right vs. left breast). Identification of IMN flow increased from 5.7% to 10.1% with the use of a deep injection technique. IMN radiotherapy was used more frequently in patients with larger tumors (15 of 188 in Tis/T1 vs. 31 of 70 in T2-T4; P<0.0001) and positive lymph nodes (17 of 91 in lymph node-negative patients vs. 28 of 66 in lymph node-positive patients; P<0.0001). In patients with T2N0 tumors (n=32), IMN radiotherapy was used more frequently with medial tumors (5 of 11 [45%]) than with lateral tumors (4 of 21 [19%]). CONCLUSIONS: The incidence of flow to the IMN documented with the current LS technique was low compared with other LS and extended radical mastectomy series. Histopathologic information was obtained for the sentinel IMN when IMN flow was identified on the LS. In the absence of histopathologic information, treatment decisions should continue to be based on clinical factors known to be correlated with occult IMN involvement.

Breast-conserving therapy (BCT) for early-stage breast cancer.

Several patient and tumor factors go into the decision process to determine whether a breast cancer patient is a good candidate for breast-conserving therapy. The patient must be seen by all disciplines before any therapeutic intervention. When used appropriately, breast-conserving therapy produces maximal disease control and improves quality of life in patients with early-stage breast cancer.

Metastatic lobular breast cancer presenting with malignant ascites: case report and review of literature.

We review the case of an elderly woman with invasive lobular breast cancer presenting as malignant ascites. This unusual presentation is discussed, as well as the options for treatment. Most invasive lobular breast cancers are hormone receptor positive and the roles of hormonal and chemotherapy are reviewed.

Postmastectomy radiotherapy: patterns of recurrence and long-term disease control using electrons.

PURPOSE: To determine the patterns of failure and prognostic factors for locoregional recurrence after postmastectomy radiotherapy (RT), using a specific electron beam technique. METHODS AND MATERIALS: A uniform electron beam was used in 323 patients with invasive breast cancer at the University of Florida Health Science Center. The patterns of disease recurrence, prognostic factors, and overall outcome were studied. RESULTS: At 10 years, the freedom from locoregional recurrence, disease-free survival, and absolute survival rate was 90%, 62%, and 55%, respectively. The 10-year disease-free survival rate for patients with 0, 1-3, and >3 positive lymph nodes was 73%, 75%, and 47%, respectively. On multivariate analysis, the three factors significantly associated with locoregional recurrence were T stage, number of involved nodes, and RT fields. Full axillary fields appeared to be beneficial (p = 0.02). Patients with positive surgical margins appeared to benefit from a mastectomy incision boost to >/=65 Gy. Finally, patients with T2N0 disease had a substantial risk of chest wall recurrence without chest wall RT. CONCLUSION: Findings include a low rate of clinically detectable locoregional recurrence. The data suggest benefits for the addition of full axillary RT in node-positive patients and chest wall RT in patients with T2N0 disease.

Breast boost: are we missing the target?

BACKGROUND: Randomized trials have shown improved local control with the use of a breast boost for patients given breast-conserving treatment for breast carcinoma. Although the use of a breast boost is routine practice, no standard technique has been established. The authors compared the commonly used clinical technique with a technique based on computed tomography (CT) imaging of surgical clips in the tumor bed. METHODS: Thirty patients underwent CT simulation for postoperative radiation treatment planning as part of breast conservation therapy. During simulation, a CT-compatible wire was placed on the patient's skin, outlining the intended electron boost field; an electron boost volume (EBV) was generated by contouring the tissue underlying the wire. Also contoured was a CT-based clinical target volume (CTV) using surgical clips and postsurgical changes in the tumor bed as a guide. A planning target volume (PTV) was generated using a 1 cm margin around the CTV. An electron beam treatment plan was generated for each technique using the FOCUS three-dimensional treatment planning system. Dose-volume histograms (DVH) were generated to determine the fraction of the PTV receiving 90% of the prescribed dose if treatment was delivered using the EBV. In addition, DVH analysis was done to determine the volume of normal tissue unnecessarily irradiated when using the EBV. RESULTS: Although the electron cone size remained unchanged in most patients for both EBV and PTV, the isocenter differed more than 1 cm in the medial-lateral direction in 5 patients and in the cephalocaudal direction in 12 patients. The en face gantry angle differed for most patients. On average, only 51% (range, 27-79%) of the PTV received 90% or more of the prescribed dose when the electron plan was generated using the EBV (P < 0.0001). Ten patients received the prescription dose to less than 50% of the PTV. Mean volume of normal tissue receiving more than 50% of prescribed dose was 64.5 cm(3) (range, 24-119 cm(3)). CONCLUSIONS: Clinical delineation of the tumor bed not only carries a significant risk of missing the target, but unnecessarily treats breast tissue that may otherwise be spared. Better delineation of the tumor bed, which optimizes coverage of the target volume and spares normal breast tissue, has the potential to improve both local control and cosmetic outcome. The authors recommend the use of surgical clips to delineate the target volume, followed by CT-based treatment planning, accounting for not only microscopic disease, but also organ motion and daily setup error.