Alice Y. Ho

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Toxicity and outcomes of thoracic re-irradiation using stereotactic body radiation therapy (SBRT)

BackgroundPatients treated for a thoracic malignancy carry a significant risk of developing other lung lesions. Locoregional control of intrathoracic recurrences is challenging due to the impact of prior therapies on normal tissues. We examined the safety and efficacy of thoracic re-irradiation using high-precision image-guided stereotactic body radiation therapy (SBRT).MethodsRecords of 39 patients with prior intra-thoracic conventionally fractionated radiation therapy (RT) who underwent SBRT for a subsequent primary, recurrent or metastatic lung tumor from 11/2004 to 7/2011 were retrospectively reviewed.ResultsMedian dose of prior RT was 61 Gy (range 30–80 Gy). Median biologically effective prescription dose (α/β = 10) (BED10) of SBRT was 70.4 Gy (range 42.6-180 Gy). With a median followup of 12.6 months among survivors, 1- and 2-year actuarial local progression-free survival (LPFS) were 77% and 64%, respectively. Median recurrence-free (RFS) and overall survival (OS) were 13.8 and 22.0 months, respectively. Patients without overlap of high-dose regions of the primary and re-irradiation plans were more likely to receive a BED10 ≥100 Gy, which was associated with higher LPFS (hazard ratio, [HR] = 0.18, p = 0.04), RFS ([HR] = 0.31, p = 0.038) and OS ([HR] = 0.25, p = 0.014). Grade 2 and 3 pulmonary toxicity was observed in 18% and 5% of patients, respectively. Other grade 2–4 toxicities included chest wall pain in 18%, fatigue in 15% and skin toxicity in 5%. No grade 5 events occurred.ConclusionsSBRT can be safely and successfully administered to patients with prior thoracic RT. Dose reduction for cases with direct overlap of successive radiation fields results in acceptable re-treatment toxicity profile.

Favorable prognosis in patients with T1a/T1bN0 triple-negative breast cancers treated with multimodality therapy

The authors evaluated the clinical characteristics, natural history, and outcomes of patients who had ≤1 cm, lymph node‐negative, triple‐negative breast cancer (TNBC).

Locoregional Outcomes of Inflammatory Breast Cancer Patients Treated With Standard Fractionation Radiation and Daily Skin Bolus in the Taxane Era

PURPOSE To assess locoregional outcomes of inflammatory breast cancer (IBC) patients who received standard fractionation radiation with daily skin bolus and taxanes as part of combined-modality therapy (CMT). METHODS AND MATERIALS We retrospectively reviewed the charts of 107 patients diagnosed with IBC between January 1995 and March 2006 who presented to our department for adjuvant radiation therapy (RT). RESULTS All patients received chemotherapy (95% anthracycline and 95% taxane), modified radical mastectomy, and RT to the chest wall and regional lymphatics using standard fractionation to 50 Gy and daily skin bolus. The RT to the chest wall was delivered via electrons (55%) or photons (45%) in daily fractions of 180 cGy (73%) or 200 cGy (27%). Scar boost was performed in 11%. A majority (84%) of patients completed the prescribed treatment. Median follow-up was 47 months (range, 10-134 months). Locoregional control (LRC) at 3 years and 5 years was 90% and 87%, respectively. Distant metastases-free survival (DMFS) at 3 years and 5 years was 61% and 47%, respectively. CONCLUSIONS Excellent locoregional control was observed in this population of IBC patients who received standard fractionation radiation with daily skin bolus and taxanes as part of combined-modality therapy. Distant metastases-free survival remains a significant therapeutic challenge.

Quantifying the impact of immediate reconstruction in postmastectomy radiation: a large, dose-volume histogram-based analysis.

PURPOSE To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. METHODS AND MATERIALS Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. RESULTS Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). CONCLUSIONS Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary determinant of target coverage and normal tissue doses.

Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival.

Mesothelin is a cell surface associated antigen expressed on mesothelial cells and in some malignant neoplasms. Mesothelin-targeted therapies are in phase I/II clinical trials. The clinicopathologic and prognostic significance of mesothelin expression in triple negative breast carcinomas (TNBC) has not been fully assessed. We evaluated the expression of mesothelin and of basal markers in tissue microarrays of 226 TNBC and 88 non-TNBC and assessed the clinicopathologic features of mesothelin-expressing breast carcinomas. Furthermore, we investigated the impact of mesothelin expression on the disease-free and overall survival of patients with TNBC. We found that mesothelin expression is significantly more frequent in TNBC than in non-TNBC (36% vs 16%, respectively; p = 0.0006), and is significantly correlated with immunoreactivity for basal keratins, but not for EGFR. Mesothelin-positive and mesothelin-negative TNBC were not significantly different by patients’ race, tumor size, histologic grade, tumor subtype, lymphovascular invasion and lymph node metastases. Patients with mesothelin-positive TNBC were older than patients with mesothelin-negative TNBC, developed more distant metastases with a shorter interval, and had significantly lower overall and disease-free survival. Based on our results, patients with mesothelin-positive TNBC could benefit from mesothelin-targeted therapies.

Bilateral implant reconstruction does not affect the quality of postmastectomy radiation therapy.

To determine if the presence of bilateral implants, in addition to other anatomic and treatment-related variables, affects coverage of the target volume and dose to the heart and lung in patients receiving postmastectomy radiation therapy (PMRT). A total of 197 consecutive women with breast cancer underwent mastectomy and immediate tissue expander (TE) placement, with or without exchange for a permanent implant (PI) before radiation therapy at our center. PMRT was delivered with 2 tangential beams + supraclavicular lymph node field (50Gy). Patients were grouped by implant number: 51% unilateral (100) and 49% bilateral (97). The planning target volume (PTV) (defined as implant + chest wall + nodes), heart, and ipsilateral lung were contoured and the following parameters were abstracted from dose-volume histogram (DVH) data: PTV D95% > 98%, Lung V20Gy > 30%, and Heart V25Gy > 5%. Univariate (UVA) and multivariate analyses (MVA) were performed to determine the association of variables with these parameters. The 2 groups were well balanced for implant type and volume, internal mammary node (IMN) treatment, and laterality. In the entire cohort, 90% had PTV D95% > 98%, indicating excellent coverage of the chest wall. Of the patients, 27% had high lung doses (V20Gy > 30%) and 16% had high heart doses (V25Gy > 5%). No significant factors were associated with suboptimal PTV coverage. On MVA, IMN treatment was found to be highly associated with high lung and heart doses (both p < 0.0001), but implant number was not (p = 0.54). In patients with bilateral implants, IMN treatment was the only predictor of dose to the contralateral implant (p = 0.001). In conclusion, bilateral implants do not compromise coverage of the target volume or increase lung and heart dose in patients receiving PMRT. The most important predictor of high lung and heart doses in patients with implant-based reconstruction, whether unilateral or bilateral, is treatment of the IMNs. Refinement of radiation techniques in reconstructed patients who require comprehensive nodal irradiation is warranted.

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update

PurposeA joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT).MethodsA recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data.RecommendationsThe panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

National Breast Reconstruction Utilization in the Setting of Postmastectomy Radiotherapy

Background Immediate breast reconstruction (IBR) is often deferred, when postmastectomy radiotherapy (PMRT) is anticipated, due to high complication rates. Nonetheless, because of robust data supporting improved health‐related quality of life associated with reconstruction, physicians and patients may be more accepting of tradeoffs. The current study explores national trends of IBR utilization rates and methods in the setting of PMRT, using the National Cancer Database (NCDB). The study hypothesis is that prosthetic techniques have become the most common method of IBR in the setting of PMRT. Methods NCDB was queried from 2004 to 2013 for women, who underwent mastectomy with or without IBR. Patients were grouped according to PMRT status. Multivariate logistic regression was used to calculate odds of IBR in the setting of PMRT. Trend analyses were done for rates and methods of IBR using Poisson regression to determine incidence rate ratios (IRRs). Results In multivariate analysis, radiated patients were 30% less likely to receive IBR (p < 0.05). The rate increase in IBR was greater in radiated compared with nonradiated patients (IRR: 1.12 vs. 1.09). Rates of reconstruction increased more so in radiated compared with nonradiated patients for both implants (IRR 1.15 vs. 1.11) and autologous techniques (IRR 1.08 vs. 1.06). Autologous reconstructions were more common in those receiving PMRT until 2005 (p < 0.05), with no predominant technique thereafter. Conclusion Although IBR remains a relative contraindication, rates of IBR are increasing to a greater extent in patients receiving PMRT. Implants have surpassed autologous techniques as the most commonly used method of breast reconstruction in this setting.

Which patients with sentinel node-positive breast cancer can avoid axillary dissection?

Sentinel lymph node (SLN) biopsy is standard care for patients with cN0 breast cancer. An extensive literature, including seven randomized trials, has established that patients with negative SLN do not require axillary dissection (ALND), that axillary local recurrence after a negative SLN biopsy is rare, that disease-free and overall survival are unaffected by the addition of ALND to SLN biopsy, and that the morbidity of SLN biopsy is substantially less than that of ALND. It is now clear that many patients with positive SLN do not require ALND. In ACOSOG Z0011, 6-year locoregional control and survival were equivalent with versus without the performance of ALND in cT1-2N0 patients with ≤2 positive SLN treated by breast conservation with whole breast radiation therapy. A small but growing body of data now suggests that ALND may not be required for selected patients outside the Z0011 eligibility criteria, specifically those treated by mastectomy (without post-mastectomy radiation therapy), by partial breast irradiation, and by neoadjuvant chemotherapy. Looking ahead, the principal goals of axillary staging, prognostication, and local control will be accomplished by SLN biopsy for a substantial majority of patients, and the role of ALND will continue to diminish.