Patterns and Incidence of Pneumonitis and Initial Treatment Outcomes with Durvalumab Consolidation Therapy after Radical Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer.

Durvalumab consolidation after chemoradiotherapy for stage III non-small cell lung cancer (NSCLC) has become the standard of care. Single-center results were examined for treatment outcomes and patterns of pneumonitis in clinical practice. Patients with stage III NSCLC who underwent chemoradiotherapy at our institution (n = 150) were included. The patients were treated with chemoradiotherapy and durvalumab consolidation (Group D, n = 69) or chemoradiotherapy alone (Group N, n = 81). The overall survival (OS), progression-free survival (PFS), and the incidence of and risk factors for 12-month pneumonitis grade ≥ 2 (G2) were investigated. Two-year OS rates were 71.6% in Group D and 52.7% in Group N (p = 0.052). Two-year PFS rates were 43.0% in Group D and 26.5% in Group N (p = 0.010), although a propensity score matched analysis showed no significant difference. The incidence of 12-month pneumonitis ≥ G2 tended to be higher in Group D than in Group N (41.9% vs. 26.3%, p = 0.080). However, there was no difference in pneumonitis ≥ G3 rates (10.5% vs. 12.6%, p = 0.657). A multivariate analysis showed that the lung volume spared from 5 Gy (VS5) < 1800 cm3 was a risk factor for pneumonitis ≥ G2 in Group D. Durvalumab consolidation showed the potential to prolong PFS without increasing the severity of pneumonitis.

Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors.

BACKGROUND: Standard treatment strategies for embryonal central nervous system (CNS) tumors have not yet been established. We treated these tumors using an original chemoradiation therapy protocol; the clinical outcomes and toxicities were retrospectively evaluated. METHODS: Twenty-four patients were enrolled including sixteen with medulloblastoma, four with supratentorial primitive neuroectodermal tumor (sPNET), three with atypical teratoid/rhabdoid tumor, and one with pineoblastoma. Immediately after diagnosis, all patients underwent surgery initially. They were then categorized as high- or average-risk groups independent of tumor type/pathogenesis. The average-risk group included patients who were aged ≥3 years at diagnosis, had non-metastatic disease at diagnosis (M0), and had undergone gross total resection. Other patients were categorized as the high-risk group; this group received more intensive treatment than the average-risk group, including high-dose chemotherapy with autologous stem-cell transplantation. All patients received craniospinal irradiation (CSI). The CSI dose was 23.4 Gy for M0 patients aged ≥5 years, 18 Gy for M0 patients aged <5 years, and 30-36 Gy for all patients with M + disease. The total dose to the primary tumor bed was 54 Gy. RESULTS: The median follow-up time was 73.5 (range, 19-118) months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 71.1 and 88.9%, respectively in the average-risk group (n = 9) and 66.7 and 71.1%, respectively in the high-risk group (n = 15). The PFS and OS rates were not significantly different between the average- and high-risk groups. In patients with medulloblastoma only, these rates were also not significantly different between the average- and high-risk groups. Three of four patients with sPNET were disease free. The height standard deviation score (SDS) was significantly decreased at the last assessment relative to that at diagnosis (P < 0.0001). The latest median height SDS was -1.6 (range, 0.9 to -4.8), and the latest median full-scale intelligence quotient (FSIQ) score was 86 (range, 59-128). The CSI doses and age at the start of radiation therapy did not influence clinical outcomes, height SDSs, and FSIQ scores. CONCLUSIONS: Our original protocol for patients with embryonal CNS tumors was feasible and yielded favorable clinical outcomes.

Radiation therapy for angiosarcoma of the scalp: treatment outcomes of total scalp irradiation with X-rays and electrons.

BACKGROUND AND PURPOSE: Wide surgical excision is the standard treatment for angiosarcoma of the scalp, but many patients are inoperable. Therefore, we investigated the outcome of radiation therapy for angiosarcoma of the scalp. PATIENTS AND METHODS: Seventeen patients with angiosarcoma of the scalp underwent radiation therapy with total scalp irradiation. Four patients had cervical lymph node metastases, but none had distant metastases. A median initial dose of 50 Gy in 25 fractions was delivered to the entire scalp. Subsequently, local radiation boost to the tumor sites achieved a median total dose of 70 Gy in 35 fractions. RESULTS: Fourteen of the 17 patients developed recurrences during the median follow-up period of 14 months after radiation therapy; 7 had recurrences in the scalp, including primary tumor progression in 2 patients and new disease in 5, and 12 patients developed distant metastases. The primary progression-free, scalp relapse-free, and distant metastasis-free rates were 86, 67, and 38 % at 1 year and 86, 38, and 16 % at 3 years, respectively. Thirteen patients died; the overall and cause-specific survival rates were both 73 % at 1 year and 23 and 44 % at 3 years, respectively. The median survival time was 16 months. There were no therapy-related toxicities ≥ grade 3. CONCLUSION: Total scalp irradiation is safe and effective for local tumor control, but a dose of ≤ 50 Gy in conventional fractions may be insufficient to eradicate microscopic tumors. For gross tumors, a total dose of 70 Gy, and > 70 Gy for tumors with deep invasion, is recommended.

Definitive radiation therapy for extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is frequently inoperable because of old age and/or coexisting disease. We therefore reviewed the efficacy and toxicity of radiation therapy for EMPD. PATIENTS AND METHODS: Fourteen patients with EMPD underwent definitive radiation therapy. Three patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 52-80.2 Gy (median=60.6 Gy) were delivered to tumor sites in 26-43 fractions (median=33 fractions). RESULTS: Four patients had developed recurrence at a median follow-up period of 47 months. The 5-year local control and disease-free rates were 71% and 63%, respectively. Two patients died of old age and renal failure at 6 and 51 months, respectively, after irradiation. The 5-year disease-free, cause-specific and overall survival rates were 46%, 100% and 79%, respectively. No therapy-related toxicities of grade 3 or greater were observed. CONCLUSION: Radiation therapy is effective and safe, and appears to offer a curative treatment option for patients with EMPD.

Treatment outcomes, growth height, and neuroendocrine functions in patients with intracranial germ cell tumors treated with chemoradiation therapy.

PURPOSE: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. METHODS AND MATERIALS: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. RESULTS: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. CONCLUSIONS: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with GCT.

Assessment of tumor hypoxia by 62Cu-ATSM PET/CT as a predictor of response in head and neck cancer: a pilot study.

OBJECTIVE: In radiotherapy and chemotherapy tumor hypoxia is recognized as a major obstacle to effective treatment. We undertook a pilot study in patients with locally advanced head and neck cancer to determine whether there is a relationship between tumor uptake of (62)Cu-ATSM and response to chemoradiotherapy. METHODS: Seventeen patients were studied using PET/CT with (62)Cu-ATSM and (18)F-FDG prior to the initiation of radiotherapy and chemotherapy. All patients had locally advanced head and neck cancer (stage III or IV). Tumor uptake in all patients was measured by region of interest analysis using the maximal standardized uptake value (SUVmax). A total dose of 50.4-70.2 Gy (median 70.2 Gy) was delivered in 29-39 fractions (median 39 fractions) to tumor. In patients with (non CR) and without (CR) residual/recurrent tumors at 2-year post irradiation, the statistical significance of the differences in tumor (62)Cu-ATSM SUVmax, T/M ratio, (18)F-FDG SUVmax and tumor volume were analyzed using Student's t test and Welch test. The relationship between clinical outcome and (62)Cu-ATSM/(18)F-FDG uptake patterns was analyzed using Kruskal-Wallis test. The correlation between SUVmax of (62)Cu-ATSM and (18)F-FDG was compared by Spearman's rank correlation test. RESULTS: Two of the 17 patients that were enrolled in our study were excluded from the final analysis. Of the 15 remaining patients, 9 patients were free of disease and 6 patients had residual/recurrent tumors. The SUVmax differed significantly (p < 0.05) between patients with or without residual/recurrent tumor on (62)Cu-ATSM PET/CT. Six of the 10 patients with tumors SUVmax >5.00 had residual/recurrent tumor, whereas all of the 5 patients with tumors SUVmax <5.00 were free of disease. There was no significant difference in FDG uptake between patients with and without residual/recurrent tumor. CONCLUSIONS: The results of this pilot study suggested that (62)Cu-ATSM uptake may be a predictive indicator of tumor response to chemoradiotherapy in patients with locally advanced head and neck cancer.

Treatment effects and sequelae of radiation therapy for orbital mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. METHODS AND MATERIALS: Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage IEA in 29 patients and stage IIEA in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. RESULTS: All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. CONCLUSIONS: Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

Role of radiotherapy as curative treatment of extramammary Paget's disease.

PURPOSE: Extramammary Paget's disease (EMPD) is a relatively rare malignancy that usually arises in the genital areas. Wide surgical excision remains the standard and most reliable curative treatment of EMPD. However, surgery is sometimes not possible, because many patients are elderly, and complete excision can be difficult owing to the tumor location. We, therefore, performed a review to determine the role of radiotherapy (RT) for EMPD. METHODS AND MATERIALS: A total of 22 patients with EMPD in their external genitalia (4 men and 18 women, age 52-94 years at RT) underwent RT with curative intent. Nine patients had regional lymph node metastases. A total dose of 45-70.2 Gy (median, 60) was delivered to the pelvis, including the tumors, in 25-39 fractions (median, 33). RESULTS: In all but 3 patients, the irradiated tumors were controlled during a follow-up period of 8-133 months (median, 42). Of the 22 patients, 13 developed recurrences, including local progression within the radiation field in 3 and lymph node and/or distant metastases outside the radiation field in 10, at 3-43 months after treatment. The 2- and 5-year local progression-free rates were 91% and 84%, respectively. Of the 22 patients, 7 patients had died at 33-73 months after RT. The cause of death was tumor progression in 4, infectious pneumonia in 2, and renal failure in 1 patient. The overall and cause-specific survival rates were 100% for both at 2 years and 53% and 73% at 5 years, respectively. No therapy-related Grade 3 or greater toxicity was observed. CONCLUSIONS: RT is safe and effective for patients with EMPD. It appears to contribute to prolonged survival as a result of good tumor control.

Geographic distribution of the incidence of adult T-cell leukemia/lymphoma and other malignancies in nagasaki prefecture, Japan.

BACKGROUND: It remains unclear whether human T-cell lymphotropic virus type-I (HTLV-I) infection is associated with an increased risk of malignancies other than adult T-cell leukemia/lymphoma. METHODS: The authors investigated the geographic distribution of the incidence of adult T-cell leukemia/lymphoma and other malignancies in Nagasaki Prefecture, Japan, where HTLV-I is endemic. The world age-standardized incidence rates of adult T-cell leukemia/lymphoma and five cancers of other sites were calculated in 15 areas, using the data from the Nagasaki Prefectural Cancer Registry (1985-97). RESULTS: The incidence of adult T-cell leukemia/lymphoma was found to be positively correlated with that of biliary tract cancer in men (person-years-weighted r = 0.49, P = 0.06) and liver cancer in women (r = 0.56, P = 0.03), but not with cancer of the stomach, lung or cervix uteri. CONCLUSIONS: The results may not support the hypothesis that HTLV-I infection is strongly associated with an increased risk of cancer of the stomach, lung or cervix uteri. The association between HTLV-I infection and cancer of the biliary tract and the possible interaction between hepatitis C virus and HTLV-I in the development of liver cancer should be evaluated by prospective cohort studies.