Impact of Regional Nodal Irradiation and Hypofractionated Whole-Breast Radiation on Long-Term Breast Retraction and Poor Cosmetic Outcome in Breast Cancer Survivors.

PURPOSE: We performed a prospective longitudinal study to determine predictors of long-term breast asymmetry in breast cancer patients treated with breast-conserving surgery and whole-breast external-beam radiotherapy (XRT). PATIENTS AND METHODS: A total of 109 patients with stage 0 to III breast cancer treated with breast-conserving surgery followed by conventional (50 Gy plus boost) or hypofractionated (39.9 Gy with simultaneous integrated boost of 48 Gy) XRT were enrolled onto 2 studies of XRT-induced skin toxicity before (baseline), during, and 1 year after XRT. Using baseline and 1-year post-XRT photographs, breast asymmetry was objectively quantified by calculating the percentage breast retraction assessment (pBRA), with larger values indicating more asymmetry. Skin thickness ratio (STRA) values were calculated using ultrasound images. Univariate and multivariate analyses were conducted to determine the relationship among STRA-, patient-, tumor-, and treatment-related factors, and pBRA. RESULTS: Seventy-one patients (65%) had more breast asymmetry (positive change in pBRA) 1 year after XRT relative to baseline. Only pre-XRT STRA was associated with a higher pre-XRT baseline pBRA in multivariate analysis (P = .02). Larger breast volume, baseline pBRA, conventionally fractionated (vs. hypofractionated) XRT, supraclavicular nodal irradiation, and higher STRA at 1 year predicted for higher long-term pBRA in the multivariate model (all P < .05). Breast volume and supraclavicular nodal irradiation were associated with the largest changes in breast asymmetry (all P < .05). CONCLUSION: This prospective longitudinal study confirmed the known impact of breast volume, surgery, and XRT on breast asymmetry. We also found that supraclavicular nodal irradiation and conventionally fractionated XRT are associated with worse cosmetic outcome 1 year after XRT.

Full axillary lymph node dissection and increased breast epidermal thickness 1 year after radiation therapy for breast cancer.

BACKGROUND: We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post-radiation therapy (RT), and now report ALND's long-term impact at 1 year. METHODS: Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post-RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast. RESULTS: A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post-RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05). CONCLUSIONS: In the setting of whole breast RT, our findings suggest that ALND has long-term repercussions on breast skin thickening.

The role of postmastectomy radiotherapy in women with pathologic T3N0M0 breast cancer.

BACKGROUND: The authors determined the impact of postmastectomy radiotherapy (PMRT) on overall survival (OS) among patients with pT3N0M0 breast cancer in the National Cancer Data Base. METHODS: A total of 3437 patients with pT3N0M0 breast cancer who initially were treated with mastectomy between 2003 and 2011 were identified. Of these women, 1644 (47.8%) received PMRT (67% treated with chest wall RT alone and 33% treated with chest wall and regional lymph node irradiation). Univariable and multivariable analyses were conducted to identify characteristics associated with PMRT and OS. In addition, propensity score matching and interaction effect testing also were performed. RESULTS: PMRT was associated with age <40 years, private insurance coverage, treatment facility location within 10 miles of the patient's home zip code, Charlson-Deyo comorbidity score of 0, tumor size ≥7 cm, and treatment with chemotherapy or hormone therapy (all P<.05). PMRT was associated with improved 5-year OS (86.3% for patients treated with PMRT vs 66.4% for patients not treated with PMRT; P<.01). In addition to PMRT (hazard ratio, 0.72; 95% confidence interval, 0.59-0.87 [P<.01]), age ≤50 years, treatment at an academic/research program, Charlson-Deyo comorbidity score of 0, tumor size <7 cm, chemotherapy receipt, and hormone therapy receipt were associated with improved OS on multivariable analyses (all P<.05). Interaction testing found that PMRT improved OS independent of age, facility type, Charlson-Deyo comorbidity score, tumor grade and size, surgical margin status, and receipt of chemotherapy or hormone therapy (all P>.1). Finally, propensity score matching analysis confirmed the impact of PMRT on OS (P = .02). It is interesting to note that regional lymph node irradiation did not improve OS versus chest wall RT alone (P = .09). CONCLUSIONS: Among patients with pT3N0M0 breast cancer in the National Cancer Data Base, PMRT was found to be associated with improved OS regardless of surgical margin status, tumor size, and receipt of systemic therapy. Cancer 2017;123:2829-39. © 2017 American Cancer Society.

Benefit of adjuvant radiotherapy after breast-conserving therapy among elderly women with T1-T2N0 estrogen receptor-negative breast cancer.

BACKGROUND: The purpose of the current study was to evaluate the impact of radiotherapy (RT) among women aged ≥ 70 years with T1-2N0 estrogen receptor (ER)-negative breast cancer using Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data. METHODS: The study included 3432 women, 2850 of whom received and 582 of whom did not receive RT after breast-conserving surgery. Outcomes were estimated by the cumulative incidence method and compared with the Gray test. The Fine and Gray subdistribution hazard regression models were used to assess the impact of RT and other variables. RESULTS: Women who received RT were more commonly aged <75 years (42% vs 16%), had T1 tumors (78% vs 65%), ductal carcinoma histology (91% vs 88%), a Charlson-Deyo Comorbidity Index of 0 (41% vs 25%), and had received chemotherapy (29% vs 12%). The 5-year cumulative incidence of mastectomy and breast cancer-specific death for patients who received versus those did not receive adjuvant RT was 4.9% and 8.3% versus 10.8% and 24.1%, respectively (P<.001). On multivariable analysis, the omission of RT was found to be an independent predictor of an increased risk of mastectomy (hazard ratio, 2.33; 95% confidence interval, 1.56-3.49). Among women aged ≥ 80 years or with T1N0 tumors, the mastectomy incidence with or without receipt of RT was 3.4% vs. 6.9%, and 5.3% vs 7.7%, respectively. CONCLUSIONS: The use of adjuvant RT after breast-conserving surgery in older women with T1-2N0 estrogen receptor-negative breast cancer is associated with a reduced incidence of future mastectomy and breast cancer death. The magnitude of benefit may be small for women aged ≥80 years or those with T1 tumors. Cancer 2016;122:3059-3068. © 2016 American Cancer Society.

Value of PET restaging after chemotherapy for non-Hodgkin's lymphoma: implications for consolidation radiotherapy.

PURPOSE/OBJECTIVE: Patients treated for non-Hodgkin's Lymphoma (NHL) frequently are restaged for response using positron emission tomography (PET) scanning. This study investigates the role of subsequent consolidation radiation therapy (CRT) based on PET response to chemotherapy. MATERIALS/METHODS: An IRB-approved database was queried for patients who underwent PET scans after chemotherapy for NHL between 1995 and 2004; 77 patients were identified. To determine benefit of CRT, overall survival and local control were assessed with median follow-up of 39.8 months (range, 2-125 months). RESULTS: Median age of patients was 53 (range, 18-82 years). Multivariate analysis adjusted for age, indolent vs. aggressive histology, and time from chemotherapy to PET revealed PET positive scans (RR = 30.5; 95%CI = 5.9, 156.4), lack of RT (RR = 5.25; 95%CI = 1.26, 21.79), and Stage III/IV presentation (RR = 4.35; 95%CI = 1.03, 20) predicted increased likelihood of recurrence. Patients with positive PET scans after chemotherapy had significantly higher risk of relapse than those with negative scans (58.1% vs. 15.2%; p < 0.0001), although not everyone with positive scans recurred. Patients with positive PET scans receiving RT were not protected from relapse (63.2% relapse with RT, 50% relapse without RT; p = 0.71); in fact, over half the relapses in patients receiving RT for persistently positive PET scans were in-field. Crude 2 year OS was significantly different between PET positive and PET negative cohorts (p < 0.01). CONCLUSIONS: While RT may control relapse in PET negative patients, NHL patients who remain PET positive after chemotherapy are not well managed by RT alone.

Refractory or relapsed Hodgkin's disease and non-Hodgkin's lymphoma: optimizing involved-field radiotherapy in transplant patients.

UNLABELLED: This study assessed efficacy, optimal dosage and timing, and toxicity of involved-field radiotherapy used in conjunction with high-dose chemotherapy and stem cell transplantation for patients with refractory/relapsed Hodgkin's disease and non-Hodgkin's lymphoma. METHODS AND MATERIALS: 306 patients with refractory or relapsed Hodgkin's disease and non-Hodgkin's lymphoma were analyzed. Forty-one patients underwent involved-field radiotherapy in conjunction with high-dose chemotherapy and bone marrow or peripheral stem cell transplantation. Thirty-three patients received involved-field radiotherapy prior to stem cell transplantation directed at symptomatic and/or bulky sites; eight patients received involved-field radiotherapy after stem cell transplantation directed at sites of persistent disease. The other 265 patients with refractory/relapsed non-Hodgkin's lymphoma and Hodgkin's disease received high-dose chemotherapy/stem cell transplantation, but not involved-field radiotherapy. Data were analyzed using Cox proportional hazards regression to determine the risk of death among patients treated with stem cell transplantation compared with that among patients treated with stem cell transplantation and involved-field radiotherapy. RESULTS: There were 124 deaths during the follow-up period, including 17% of the patients treated with involved-field radiotherapy and 44.2% of the patients receiving chemotherapy without involved-field radiotherapy. Multivariate analysis found that patients who did not receive involved-field radiotherapy were 2.09 times more likely to die during the follow-up period than patients who received involved-field radiotherapy (P = 0.066; adjusted for age, stem cell transplantation type, stage I/II vs stage III/IV, refractory vs relapsed, and Hodgkin's disease vs non-Hodgkin's lymphoma). When patients were treated with involved-field radiotherapy prior to stem cell transplantation, 27 (79.4%) of the 34 patients achieved local control; when involved-field radiotherapy followed stem cell transplantation, 6 (85.7%) of the 7 patients experienced local control. Timing of involved-field radiotherapy prior to or following stem cell transplantation did not affect patient survival. Five of the 41 patients treated with involved-field radiotherapy developed toxicity subsequent to treatment. All but one of these patients had been treated with doses greater than 30 Gy. CONCLUSIONS: Although of borderline significance in this small sample, results of this study suggest that patients who receive involved-field radiotherapy in conjunction with stem cell transplantation may have increased survival when compared with patients who do not receive involved-field radiotherapy. Further follow-up of this cohort is necessary to confirm these findings.

Management of xerostomia related to radiotherapy for head and neck cancer.

Xerostomia is a permanent and devastating sequela of head and neck irradiation, and its consequences are numerous. Pharmaceutical therapy attempts to preserve or salvage salivary gland function through systemic administration of various protective compounds, most commonly amifostine (Ethyol) or pilocarpine. When these agents are ineffective or the side effects too bothersome, patients often resort to palliative care, for example, with tap water, saline, bicarbonate solutions, mouthwashes, or saliva substitutes. A promising surgical option is the Seikaly-Jha procedure, a method of preserving a single submandibular gland by surgically transferring it to the submental space before radiotherapy. Improved radiation techniques, including intensity-modulated radiotherapy and tomotherapy, allow more selective delivery of radiation to defined targets in the head and neck, preserving normal tissue and the salivary glands. Acupuncture may be another option for patients with xerostomia. All of these therapies need to be further studied to establish the most effective protocol to present to patients before radiotherapy has begun.