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The interest in combining radiation therapy (RT) with immunotherapy is increasing. We investigated the significance of lymphopenia in patients receiving immunotherapy for non-small cell lung cancer (NSCLC), and the factors associated with treatment-related lymphopenia, with particular emphasis on RT.In this retrospective single institution study, 268 patients with advanced NSCLC received immunotherapy, of whom 146 received RT. Lymphopenia was defined as an absolute lymphocyte count1000 cells/mm.At median 6.4 months of follow-up, patients with peri-immunotherapy lymphopenia (n = 146; 54.5%) showed significantly poorer progression-free survival (PFS) (median PFS: 2.2 vs 5.9 months, P.001) and overall survival (OS) (median OS: 5.7 vs 12.1 months, P.001). On multivariate analysis, peri-immunotherapy lymphopenia remained a significant prognostic factor for both PFS and OS. RT significantly increased peri-immunotherapy lymphopenia with an odds ratio (OR) of 1.91 (P = .025). Factors associated with the development of RT-associated lymphopenia included multiple courses (OR, 3.78; P.001), multiple irradiated sites (OR, 4.77; P = .018), and higher dose (≥50 Gy) (OR, 3.75; P = .004). Conversely, stereotactic body RT/radiosurgery reduced the risk (OR 0.21; P = .002).Lymphopenia was indicative of poor prognosis in NSCLC patients receiving immunotherapy and was significantly associated with more intensive RT. Choosing appropriate RT regimens and techniques may be essential in reducing lymphopenia. Promising results are expected in the era of precision RT.

To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy.Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%.The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively.Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.

Purpose To analyze risk factors and the dose–effect relationship for osteoradionecrosis (ORN) of the mandible after radiotherapy of oral and oropharyngeal cancers. Materials and Methods One-hundred ninety-eight patients with oral (45%) and oropharyngeal cancer (55%) who had received external radiotherapy between 1990 and 2000 were retrospectively reviewed. All patients had a dental evaluation before radiotherapy. The median radiation dose was 60 Gy (range, 16–75 Gy), and the median biologically effective dose for late effects (BED late ) in bone was 114 Gy 2 (range, 30–167 Gy 2 ). Results The frequency of ORN was 13 patients (6.6%). Among patients with mandibular surgery, eight had ORN at the surgical site. Among patients without mandibular surgery, five patients had ORN on the molar area of the mandible. The median time to ORN was 22 months (range, 1–69 months). Univariate analysis revealed that mandibular surgery and Co-60 were significant risk factors for ORN ( p = 0.01 and 0.04, respectively). In multivariate analysis, mandibular surgery was the most important factor ( p = 0.001). High radiation doses over BED 102.6 Gy 2 (conventional dose of 54 Gy at 1.8 Gy/fraction) were also a significant factor for ORN ( p = 0.008) and showed a positive dose–effect relationship in logistic regression ( p = 0.04) for patients who had undergone mandibular surgery. Conclusions Mandibular surgery was the most significant risk factor for ORN of mandible in oral and oropharyngeal cancers patients. A BED of 102.6 Gy 2 or higher to the mandible also significantly increases the risk of ORN.

Purpose To evaluate the feasibility of synchronous treatment of multiple metastatic lesions by helical tomotherapy. Methods and Materials Forty-two patients with multiple metastatic lesions were treated by helical tomotherapy from April 2006 to February 2007. Among these patients, 21 had metastatic bone disease. Subjective pain response was assessed using the visual analogue scales, and morbidity was evaluated by Common Terminology Criteria for Adverse Events v3.0. The correlation between the percentage of red bone marrow in the radiation field and the severity of leukocytopenia was analyzed. Results The median age was 57 years. Radiation dose to the gross tumor volume was 30–84 Gy, with a median fractional size of 3 Gy. Mean treatment time was 16 min and 1 sec. Treatment time and fraction size were modified because of poor performance status or hematologic toxicity in two patients. With regard to palliative effects for bone metastasis, 16 patients (76.2%) experienced positive pain relief. Four patients had Grade III leukocytopenia, and three had Grade IV leukocytopenia. In the multivariate logistic regression, red marrow percentage was the independent risk factor most associated with Grade III/IV leukocytopenia ( p = 0.014). The tolerance cutoff point of red bone marrow was 26.8%, with a sensitivity and specificity of 85.7% and 85.7%, respectively. Conclusions Helical tomotherapy was effective for symptom palliation and was feasible for patients with multiple metastatic diseases. The volume of red bone marrow, as well as performance status, must be taken into account to determine optimal treatment.

To determine the role of adjuvant external-beam radiotherapy (EBRT) in the management of patients with well-differentiated thyroid cancer invading the trachea.Of 1,098 thyroid cancer patients, 68 (6%) were found to have tracheal invasion, and they all received "shave" excision of the tracheal cartilage. Among them, 12 patients had no postoperative residuum, 43 patients had microscopic residuum, and 13 patients had macroscopic residuum. All patients were divided into two groups according to treatment modality with or without EBRT; (1) the control group (n = 43) and (2) the EBRT group (n = 25).The locoregional recurrence rate for EBRT patients was much lower than that of control patients (51% for the control group vs. 8% for the EBRT group) (p0.01). The 10-year local progression-free survival rate for the EBRT group was significantly better than that of the control group (89% in the EBRT group vs. 38% in the control group) (log-rank, p0.01). The use of adjuvant EBRT after conservative surgery was an independent prognostic factor in univariate and multivariate analyses.External-beam radiotherapy was found to be effective, particularly in patients with thyroid cancer invading the trachea with microscopic or gross residuum after conservative surgery.

Purpose To determine the differential expression of cyclooxygenase-2 (COX-2) in patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the uterine cervix and the prognostic significance of COX-2 expression in these histologic types. Methods and materials A total of 105 International Federation of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were screened for COX-2 expression immunohistochemically. COX-2 expression was determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21). To determine the clinical significance of COX-2 expression by histologic type, the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n = 64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2 positive (n = 12). The clinical response to treatment, patterns of treatment failure, and survival data by COX-2 expression were compared for these two major histologic types. Univariate and multivariate analyses were performed to identify the prognostic factors influencing survival. Results Immunohistochemical examination showed that COX-2 expression was more frequently observed in ADC than in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important predictor of treatment response, irrespective of the histologic type. All COX-2–negative patients achieved complete remission after initial treatment; 17% of SCC patients and 33% of ADC patients with COX-2 expression did not have complete remission after the initial treatment. The incidence of local failure for those with COX-2 expression was significantly greater than for COX-2–negative patients, regardless of histologic type. With a minimal follow-up of 60 months, the overall 5-year actuarial survival rate for SCC and ADC patients was 79% and 62%, respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic type, COX-2–positive patients had an unfavorable prognosis. The overall 5-year actuarial survival rate was 57% for COX-2–positive patients and 83% for COX-2–negative patients (p = 0.001). When patients were stratified into the four groups according to histologic type and COX-2 expression status, ADC/COX-2–positive patients had the worst prognosis, with an overall 5-year actuarial survival rate of 49% compared with 78% for ADC/COX-2–negative patients, 62% for SCC/COX-2–positive, and 84% for SCC/COX-2–negative patients (p = 0.007, log–rank test). Irrespective of histologic type, COX-2 expression was an independent prognostic factor by univariate and multivariate analyses. Conclusion In uterine cervical cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC patients. COX-2 expression was also identified as a major determiner of a poor response to treatment and of an unfavorable prognosis, irrespective of the histologic type, reflecting the importance of the COX-2 protein in the acquisition of biologic aggressiveness and more malignant phenotype or increased resistance to the standard chemotherapy and radiotherapy in both histologic types. Given these observations, we believe that that ADC/COX-2–positive patients might be appropriate candidates for future trials of selective COX-2 inhibitor adjunctive therapy.