Michelle S. Ludwig

Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial

IMPORTANCE The most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain. OBJECTIVE To assess acute and 6-month toxic effects and quality of life (QOL) with conventionally fractionated WBI (CF-WBI) vs hypofractionated WBI (HF-WBI). DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized trial of CF-WBI (n = 149; 50.00 Gy/25 fractions + boost [10.00-14.00 Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56 Gy/16 fractions + boost [10.00-12.50 Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended; 76% of study participants (n = 217) were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of 6 months. INTERVENTIONS Administration of CF-WBI or HF-WBI. MAIN OUTCOMES AND MEASURES Physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). All analyses were intention to treat, with outcomes compared using the χ2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS Of 287 participants, 149 were randomized to CF-WBI and 138 to HF-WBI. Treatment arms were well matched for baseline characteristics, including FACT-B total score (HF-WBI, 120.1 vs CF-WBI, 118.8; P = .46) and individual QOL items such as somewhat or more lack of energy (HF-WBI, 38% vs CF-WBI, 39%; P = .86) and somewhat or more trouble meeting family needs (HF-WBI, 10% vs CF-WBI, 14%; P = .54). Maximum physician-reported acute dermatitis (36% vs 69%; P < .001), pruritus (54% vs 81%; P < .001), breast pain (55% vs 74%; P = .001), hyperpigmentation (9% vs 20%; P = .002), and fatigue (9% vs 17%; P = .02) during irradiation were lower in patients randomized to HF-WBI. The rate of overall grade 2 or higher acute toxic effects was less with HF-WBI than with CF-WBI (47% vs 78%; P < .001). Six months after irradiation, physicians reported less fatigue in patients randomized to HF-WBI (0% vs 6%; P = .01), and patients randomized to HF-WBI reported less lack of energy (23% vs 39%; P < .001) and less trouble meeting family needs (3% vs 9%; P = .01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (odds ratio [OR], 0.39; 95% CI, 0.24-0.63) and trouble meeting family needs (OR, 0.34; 95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE Treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy. These findings should be communicated to patients as part of shared decision making. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01266642.

Treatment Compliance and Outcomes for Women With Locoregionally Advanced Cervical Cancer Treated in a Safety Net Health System.

Objective This study aims to assess treatment compliance among women undergoing definitive chemoradiation with weekly cisplatin for cervical cancer within a safety net health system and to quantify the impact of chemotherapy compliance on outcomes. Materials and Methods All women who were treated for International Federation of Gynecology and Obstetrics stage IB2 to stage IVA cervical cancer between April 2008 and May 2014 were identified. Treatment delays were attributed to toxicity, comorbid conditions, or system issues, or categorized as patient-initiated. Disease-free survival and overall survival of women who received fewer than 6 versus 6 or more doses of weekly cisplatin 40 mg/m2 were compared using Kaplan-Meier analyses. Results One hundred nineteen women (mean [SD] age, 48.5 [11.8] years) were identified. Most women (n = 112; 94.1%) completed definitive radiotherapy, requiring a mean (SD) of 56.5 (20.1) days. Sixty-four women (57.1%) completed definitive radiotherapy in 56 days or less. Only 44 women (36.4%) received 6 or more cycles of cisplatin. Of 122 delayed cycles, reasons for delay were as follows: grade 2 or higher toxicity (n = 70; 57.4%), medical comorbidity (n = 12; 9.8%), system issues (n = 9; 7.4%), and patient-initiated (n = 14; 11.5%). Multiple issues complicated treatment for 3 doses (2.5%). Reasons for delay were not documented in 14 doses (11.5%). Among patients who received 6 or more cycles, disease-free survival improved by 17.4 months (mean [SD], 61.1 [3.7] vs 43.7 [4.3] months, P = 0.002) and overall survival improved by 8.6 months (mean [SD], 68.7 [2.3] vs 60.1 [3.7] months, P = 0.011). Conclusions Higher rates of toxicity and psychosocial barriers to chemotherapy compliance adversely impact survival among women who seek care in low-resource settings. In our population, administration of all 6 cycles of cisplatin was necessary for optimal survival benefit. Future efforts to improve cervical cancer outcomes should address preventable reasons for treatment delays among underinsured or uninsured individuals.

Assessing the Optimum Use of Androgen-Deprivation Therapy in High-Risk Prostate Cancer Patients Undergoing External Beam Radiation Therapy

The optimum use of androgen deprivation therapy (ADT) in high-risk prostate cancer patients has not been defined in the setting of dose-escalated external beam radiation therapy. A retrospective analysis of 1,290 patients with high-risk prostate cancer from June 1987 through March 2010 treated with external beam radiation therapy was performed. Median follow-up was 7.2 years, and 797 patients received ADT, with 384 patients experiencing a biochemical failure and 145 with distant metastasis. ADT was associated with lower risk of biochemical failure and distant metastasis than no ADT after adjusting for age, prostate-specific antigen (PSA), Gleason score, year of diagnosis, tumor stage, and radiation dose. ADT was associated with a greater reduction in biochemical failure in the low-dose radiation group than in the high-dose group. Patients with >24 months of ADT had a lower risk of PSA failures than those with <24 months. ADT was associated with decreased risk of biochemical failure and distant metastasis in all patients. The effect of ADT on reducing risk of biochemical failure was greater among men with low-dose radiation. There was a benefit in PSA and distant metastasis-free survival with >24 months of ADT in all patients who received ADT.