Acute toxicity outcomes and dosimetric implications from incidental irradiation of adjacent tissues in tangent field hypofractionated breast radiotherapy.

PURPOSE: Adjacent tissues-in-beam (TIB) may receive substantial incidental doses within standard tangent fields during hypofractioned whole breast irradiation (HF-WBI). To characterize the impact of dose to TIB, we analyzed dosimetric parameters of TIB and associated acute toxicity. MATERIALS AND METHODS: Plans prescribed to 40.5 Gy/15 fractions from 4/2016-1/2018 were evaluated. Structures of interest were contoured: (1) TIB: all tissues encompassed by plan 30% isodose lines, (2) breast, (3) non-breast TIB (nTIB): TIB minus contoured breast. Volumes of TIB, breast, and nTIB receiving 100%-107% of prescription dose (V100-V107) were calculated. Twelve patient- and physician-reported acute toxicities were prospectively collected weekly. Correlations between volumetric and dosimetric parameters were assessed. Uni- and multivariable logistic regressions evaluated toxicity grade changes as a function of TIB, breast, and nTIB V100-V107 (in cm3). RESULTS: We evaluated 137 plans. Breast volume was positively correlated with nTIB and nTIB V100 (rho = 0.52, rho = 0.30, respectively, both p < 0.001). V107 > 2 cm3 were noted in 14% of breast and 21% of nTIB volumes. On multivariable analyses, increasing breast and nTIB V100 significantly raised odds of grade 2+ dermatitis and burning/twinging pain, respectively; increasing nTIB V105 elevated odds of hyperpigmentation and burning pain; and increasing nTIB V107 raised odds of burning pain. Threshold volumes for >6-fold odds of developing burning pain were TIB V105 > 100 cm3 and V107 > 5 cm3. CONCLUSIONS: For HF-WBI, doses to nTIB over the prescription predicted acute toxicities independent of breast doses. These data support inclusion of TIB as a region of interest in treatment planning and protocol design.

Adjuvant radiation for early stage endometrial cancer with lymphovascular invasion.

OBJECTIVE: To determine the impact of the decrease in use of postoperative pelvic external beam radiation (EBRT) in favor of intravaginal RT (IVRT) alone in patients with early stage endometrial cancer who had lymphovascular invasion (LVI). METHODS: Between 11/1988 and 5/2005, 126 patients treated with simple hysterectomy and postoperative RT had a final pathologic diagnosis of stage IB-IIB adenocarcinoma of endometrioid histology with documented LVI. The patients were divided into two groups based on the era of treatment, (early era: 1988-1996, vs. late era: 1997-2005), in order to best capture the shift away from the routine use of EBRT in favor of surgical staging and IVRT. RESULTS: Of the 126 patients, 35% (n=44) were treated in the early era and 65% (n=82) in the late era. The two groups were balanced in regards to age, race, depth of myometrial invasion, histologic grade, and cervical involvement. Significantly more patients had surgical staging and received IVRT alone in the late than early era (p=0.0001, 0.004, respectively). The rate of pelvic control was 93% for the early era compared to 97% for latter era (p=0.3). There was no significant impact of the treatment era on vaginal control, disease-free survival, or overall survival. CONCLUSIONS: These data suggest that the mere presence of LVI need not trigger the use of pelvic EBRT. Instead, the decision on whether to omit EBRT in patients with LVI should be made in the context of a patient's competing risk factors and comorbid conditions.

Whole neuraxis irradiation to address central nervous system relapse in high-risk neuroblastoma.

BACKGROUND: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). METHODS: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); one patient in the non-CSI cohort received IO-RIT. RESULTS: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. CONCLUSIONS: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.

Accelerated whole breast irradiation with intensity-modulated radiotherapy to the prone breast.

PURPOSE: Whole breast irradiation (WBI) is the standard of care for patients with early-stage breast cancer who opt for breast conservation. After a randomized trial demonstrated equivalent cosmesis and disease control with accelerated WBI (AWBI), our institution began to offer AWBI to appropriate patients. The aim of this study was to examine our unique experience with AWBI using prone positioning and simplified intensity-modulated radiotherapy (IMRT) planning with a sequential boost to the tumor bed. METHODS AND MATERIALS: We identified 356 patients who had been treated with prone WBI using IMRT in our department between January 2004 and December 2006. Of these, 128 (36%) patients had received AWBI (representing 131 treated breasts), consisting of 16 daily fractions of 265 cGy to a total dose of 4,240 cGy followed by a conventionally fractionated boost. RESULTS: Patients who opted for AWBI were similar demographically to the patients undergoing conventional WBI. In the AWBI cohort, 83% of the patients had Stage T1 disease and 22% had nodal involvement (N1). The tumors were estrogen receptor-positive, progesterone receptor-positive and Her-2/Neu-amplified in 82%, 69%, and 11%, respectively. The median duration of AWBI plus a boost was 29 days, and no patient required a toxicity-related treatment break. No Grade 3 or greater acute toxicity developed. At a median follow-up of 18 months, one ipsilateral breast recurrence developed that was salvaged with mastectomy and immediate reconstruction. CONCLUSION: AWBI to the prone breast using simplified IMRT with a sequential boost offers women requiring breast-only adjuvant radiotherapy an abbreviated treatment with early tumor control and cosmesis comparable to that with standard fractionation.

Chemoprevention of colorectal cancer in ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis (UC) are at greater risk of developing colorectal cancer (CRC) than the general population. Both duration and extent of UC are important risk factors for CRC, as is the presence of primary sclerosing cholangitis, family history of CRC, and (in some studies) early age at diagnosis of UC. Efforts to reduce this risk have focused on colonoscopic surveillance as the best alternative to the more definitive, but less appealing, approach of prophylactic colectomy. However, spurred on by findings in the sporadic CRC literature, there has been a growing interest in a possible role for chemoprevention of CRC in patients with UC. EMPIRICAL STUDIES: Published evidence to date indicates that 5-aminosalicylic acid agents are protective against the development of dysplasia and CRC. Oral, but not topical, steroids also appear to be chemoprotective, but their chronic use cannot be recommended for this indication. Ursodeoxycholic acid has been shown to reduce the risk of neoplasia in UC patients with primary sclerosing cholangitis. Evidence suggests, but does not prove, that folic acid is chemopreventive in patients with UC. Further studies are needed to fully define the chemoprotective role of these and other agents.