Total Marrow Lymphoid Irradiation/Fludarabine/ Melphalan Conditioning for Allogeneic Hematopoietic Cell Transplantation.

Reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HCT) can reduce morbidity and mortality, but patients with advanced disease may require alternative approaches. In an initial report of RIC with fludarabine (FLU) and melphalan (MEL) with total marrow lymphoid irradiation (TMLI) in HCT for advanced hematologic malignancies in 33 patients, we found that the addition of TMLI to RIC was feasible and safe. Here we report long-term outcomes for these patients. This prospective study included 61 patients treated with TMLI to a dose of 12 Gy (1.5 Gy twice daily for 4 days), FLU (25 mg/m2/day for 5 days), and MEL (140 mg/m2/day for 1 day). Overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were measured from the date of HCT. Survival outcomes were analyzed using Kaplan-Meier analysis. Patients were categorized as low/intermediate or high/very high risk using the Disease Risk Index. The median follow-up was 7.4 years. The majority of patients had acute leukemia (72%); 49% had high/very high-risk disease. The median patient age was 55 years (range, 9-70 years). Two-year OS, EFS, CIR, and NRM were 54% (95% confidence interval [CI], 41%-66%), 49% (95% CI, 36%-61%), 21% (95% CI, 13%-35%), and 30% (95% CI, 20%-43%), respectively. Five-year OS, EFS, CIR, and NRM were 42% (95% CI, 30%-54%), 41% (95% CI, 28%-53%), 26 (95% CI, 17%-40%), and 33% (95% CI, 23%-47%, respectively). Acute (any grade) and chronic (limited or extensive) graft-versus-host disease occurred in 69% and 74% of patients, respectively. The most common toxicity was mucositis. The addition of TMLI to FLU/MEL conditioning was well tolerated, with favorable outcomes. Dosage escalation of TMLI or other modifications may be needed to improve disease control.

Outcomes for patients with cervical cancer treated with extended-field intensity-modulated radiation therapy and concurrent cisplatin.

OBJECTIVE: To evaluate disease outcomes and toxicity in patients with cervical cancer treated with extended-field intensity-modulated radiotherapy. MATERIALS AND METHODS: We included all patients treated with extended-field intensity-modulated radiotherapy and concurrent weekly cisplatin from 2003 to 2010 at 2 institutions. Overall survival and disease-free survival were estimated using Kaplan-Meier method. Locoregional failure (LRF), distant failure, and competing mortality were calculated using cumulative incidence functions. Acute and late toxicity were graded using Common Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS: The study included 21 patients, 14 and 20 of which had positive para-aortic and pelvic nodes, respectively. The median follow-up was 22 months. Eighteen-month overall survival and disease-free survival were 59.7% (95% confidence interval [CI], 41.2%-86.4%) and 42.9% (95% CI, 26.2%-70.2%). Eighteen-month cumulative incidences of LRF, distant failure, and competing mortality were 9.5% (95% CI, 1.5-26.8%), 42.9% (95% CI, 21.3-62.9%), and 4.8% (95% CI, 0.3-20.2%), respectively. Eighteen-month cumulative incidences of late grade 3 or higher-grade genitourinary and gastrointestinal toxicity were 4.8% (95% CI, 0.2%-20.3%) and 0%, respectively. CONCLUSIONS: Intensity-modulated extended-field radiotherapy was associated with low rates of late toxicity and LRF. High rates of distant failure indicate that this group of patients could benefit from intensified systemic therapy.

Ovarian cancer: Deaf and hearing women's knowledge before and after an educational video.

Members of the Deaf community report language and cultural barriers to accessing health information and care. This study evaluated whether an ovarian cancer education video in American Sign Language with English captioning and voice-over could close the anticipated knowledge gap between Deaf and hearing women's cancer knowledge. Consented Deaf (n = 55) and hearing (n = 52) women's General, Ovarian, and Total Cancer Knowledge were assessed before and after viewing the video. At baseline, hearing women demonstrated significantly higher General, Ovarian, and Total Cancer Knowledge scores than Deaf women. By the post-test, all of Deaf women's knowledge scores had increased, closing the baseline gap. However, hearing women's post-video knowledge had also increased, thereby creating a new knowledge gap. The ovarian cancer education video offers an effective method to increase ovarian and general cancer knowledge for Deaf and hearing women.

Intensity-modulated Radiation Therapy for Anal Cancer: Results From a Multi-Institutional Retrospective Cohort Study.

OBJECTIVES: To assess toxicity and efficacy of intensity-modulated radiation therapy (IMRT) for anal cancer. METHODS: Records of 152 patients were reviewed retrospectively from multiple institutions. Data on disease control and toxicity were collected as well as patient and treatment characteristics. Acute (<6 mo) and late (≥6 mo) severe toxicity (grade ≥3) were graded. Four patients were excluded due to the presence of metastatic disease or stage TX. Late toxicity data were available for 120 patients. RESULTS: Median cumulative IMRT dose was 51.25 Gy (median, 28 fractions). All but 2 patients received chemotherapy. With median follow-up of 26.8 months, local control at 3 years was 87%, worse for patients with T3-T4 than T1-T2 disease on univariate analysis (79% vs. 90%; P=0.04). Regional control, distant control, and overall survival were 97%, 91%, and 87%, respectively, at 3 years. Nodal status was associated with regional control, distant control, and overall survival (P<0.01 for each). Most common severe acute toxicity was hematologic (41%), skin (20%), and gastrointestinal tract (11%). Two grade 5 toxicities occurred (hematologic and gastrointestinal tract). Severe late toxicity affected skin (1%) and gastrointestinal tract (3%). CONCLUSIONS: IMRT with chemotherapy resulted in excellent local control. Although T stage predicted worse local control, most T3-T4 disease was controlled with IMRT. Nodal status predicted regional and distant control and overall survival. Severe toxicity was acceptable.

Correlation between radiation dose to ¹8F-FDG-PET defined active bone marrow subregions and acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy.

PURPOSE: To test the hypothesis that radiation dose to (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET)-defined active bone marrow (BM(ACT)) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. METHODS AND MATERIALS: The conditions of 26 women with cervical cancer who underwent (18)F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM(ACT) was defined as the subregion of total bone marrow (BM(TOT)) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM(INACT)) was defined as BM(TOT) - BM(ACT). Generalized linear modeling was used to test the correlation between BM(ACT) and BM(INACT) dose-volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). RESULTS: Increased BM(ACT) mean dose was significantly associated with decreased log(WBC) nadir (ß = -0.04; 95% CI, -0.07 to -0.01; p = 0.009), decreased log(ANC) nadir (ß = -0.05; 95% CI, -0.08 to -0.02; p = 0.006), decreased hemoglobin nadir (ß = -0.16; 95% CI, -0.27 to -0.05; p = 0.010), and decreased platelet nadir (ß = -6.16; 95% CI, -9.37 to -2.96; p < 0.001). By contrast, there was no association between BM(INACT) mean dose and log(WBC) nadir (ß = -0.01; 95% CI, -0.06 to 0.05; p = 0.84), log(ANC) nadir (ß = -0.03; 95% CI, -0.10 to 0.04; p = 0.40), hemoglobin nadir (ß = -0.09; 95% CI, -0.31 to 0.14; p = 0.452), or platelet nadir (ß = -3.47; 95% CI, -10.44 to 3.50; p = 0.339). CONCLUSIONS: Irradiation of BM subregions with higher (18)F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM(ACT) subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BM(ACT).

The role of positron emission tomography following radiosurgical treatment of malignant lung lesions.

OBJECTIVE: To establish response patterns in PET following stereotactic body radiotherapy (SBRT) of malignant lung lesions. METHODS: Patients with malignant lung lesions treated with SBRT were retrospectively reviewed. All patients received 40-52 Gy in three to five equal fractions. An independent, blinded radiologist reassessed all 18F-fluoro-deoxy-glucose PET/computed tomography scans to determine the tumor maximum standardized uptake value (SUVmax) and size changes. RESULTS: Thirty-nine patients were included in this study. Of the 47 lesions treated, there were 22 primary and 25 metastatic lung lesions. In total, 86 PET/computed tomography studies were reviewed. The mean SUVmax values decreased markedly and stabilized after 6 months following the treatment of primary lesions. Metastatic lesions showed greater variability, with an overall increase in SUVmax values until 6 months and decrease thereafter. Of the eight local failures, the mean SUVmax and size change from nadir values to biopsy-proven failure were 117 and 215%; however, it was difficult to measure the size of five lesions because of fibrotic changes. Statistical analysis revealed metastatic tumors to be associated with poorer local control (P=0.028). No correlation was found between size or pretreatment SUVmax and outcome. CONCLUSION: Anticipated SUVmax and size patterns following SBRT remain a challenge due to surrounding tissue reactions. Nonetheless, marked SUVmax changes can aid in determining local failure. Increases in size were also observed in local failures; however, localized fibrosis challenges its utility in distinguishing failures from a normal tissue response. A larger series needs to be examined to better establish the correlation of PET responses to overall survival and local control.

Optimized planning target volume for intact cervical cancer.

PURPOSE: To model interfraction clinical target volume (CTV) variation in patients with intact cervical cancer and design a planning target volume (PTV) that minimizes normal tissue dose while maximizing CTV coverage. METHODS AND MATERIALS: We analyzed 50 patients undergoing external-beam radiotherapy for intact cervical cancer using daily online cone-beam computed tomography (CBCT). The CBCTs (n = 972) for each patient were rigidly registered to the planning CT. The CTV was delineated on the planning CT (CTV(0)) and the set of CBCTs ({CTV(1)-CTV(25)}). Manual (n = 98) and automated (n = 668) landmarks were placed over the surface of CTV(0) with reference to defined anatomic structures. Normal vectors were extended from each landmark, and the minimum length required for a given probability of encompassing CTV(1)-CTV(25) was computed. The resulting expansions were used to generate an optimized PTV. RESULTS: The mean (SD; range) normal vector length to ensure 95% coverage was 4.3 mm (2.7 mm; 1-16 mm). The uniform expansion required to ensure 95% probability of CTV coverage was 13 mm. An anisotropic margin of 20 mm anteriorly and posteriorly and 10 mm superiorly, inferiorly, and laterally also would have ensured a 95% probability of CTV coverage. The volume of the 95% optimized PTV (1470 cm(3)) was significantly lower than both the anisotropic PTV (2220 cm(3)) and the uniformly expanded PTV (2110 cm(3)) (p < 0.001). For a 95% probability of CTV coverage, normal lengths of 1-3 mm were found along the superior and lateral regions of CTV(0), 5-10 mm along the interfaces of CTV(0) with the bladder and rectum, and 10-14 mm along the anterior surface of CTV(0) at the level of the uterus. CONCLUSION: Optimizing PTV definition according to surface landmarking resulted in a high probability of CTV coverage with reduced PTV volumes. Our results provide data justifying planning margins to use in practice and clinical trials.