Long-Term Results of Two Novel Weekly High Dose Palliative Radiotherapy Schedules in Un-Resectable or Metastatic Breast Cancers: Should We Clinically Chase Statistical Significance?

Abstract

<h3>Purpose/Objective(s)</h3> In a developing country like India, large fungating breast cancers are not uncommon. This causes much deterioration in the quality of life attributed to the pain, growth of maggots, bleeding and discharge from the tumor. Surgery is often not feasible, and chemotherapy hardly brings any response in such aggressive lesions. Our initial results were presented in the last two consecutive ASTRO conferences. Our first paper showed the feasibility and safety of extreme hypo-fractionated radiotherapy (8 Gy weekly x 5 fractions) while the second one compared the toxicity and response outcomes of 40 Gy (8 Gy weekly x 5 fractions) versus 24 Gy (8 Gy x 3). This paper presents the long-term local control and survival rates between the two groups. <h3>Materials/Methods</h3> A total of 54 patients were enrolled in the study. 24 patients received 5 fractions of weekly 8 Gy to the involved breast, while 30 patients received 3 fractions of the same dose. Early and late toxicities were assessed using RTOG toxicity criteria and Harvard 4-point cosmesis respectively. All patients were planned with tangential photon beams, ensuring that the lungs and the heart are outside our treatment field. <h3>Results</h3> Out of the fifty-four patients, 45 (83%) patients were upfront metastatic, while the remaining were unresectable post-neoadjuvant chemotherapy. Thirty-eight (70%) of the patients were hormone receptor-negative, 23 (42%) patients were Her 2 Neu positive which were almost equally distributed between both arms. Overall, 44 patients (81%) had extensive skin involvement including ulcerations, fungating mass, extensive peud' orange and satellite nodules. All these patients were treated with bolus over the skin. The median largest size was 8cm (3.3cm-16cm). 25 patients (46%) succumbed to their disease, within a year of treatment, as expected in such an aggressive cohort. As reported earlier, 52% of the patients had greater than grade 2 dermatitis in the 40 Gy arm versus none of the patients who had dermatitis grade 2 or above in the 24 Gy arm (p=0.051). Again, as reported earlier, the cosmesis was significantly worse in the 40 Gy arm with 25 % of patients reporting fair or poor cosmesis as compared to none in the 24 Gy arm (p=0.052). Nine (37%) progressed in the 40 Gy arm, versus 16 (53%) in the 24 Gy arm with a median progression-free survival of 11.3months versus 13.6 months, favoring the arm with 40 Gy (p=0.04). There was a trend to increased overall survival in the 40 Gy arm (25 months versus 18 months), although this was not statistically significant (p=0.5). <h3>Conclusion</h3> This unique study compares two novel high doses of palliative radiotherapy for fungating, unresectable and chemo-resistant malignancies of the breast. The 24 Gy regimen can be safely used, with minimal concerns of toxicity and cosmesis. Although the toxicities and deterioration of cosmesis were higher for the 40 Gy arm, the statistically significant local disease control may warrant the use of this higher dose which may be individualized based on the size and nature of the lesion.