Search

OBJECTIVE An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS Eligible patients were adults with supratentorial GBMs, 16–75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry)

Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account.

We reviewed the outcomes of glioma patients enrolled in a prospective observational registry study of proton beam therapy (PBT) in Japan. The inclusion criteria were glioma patients registered in the Electronic Data Capture system, the Proton-net, between May 2016 and July 2019. Data on patient characteristics, treatments, late adverse events, survival status, recurrence and secondary tumors were extracted and statistically analyzed. The primary endpoint was the overall survival (OS) rate, and the secondary endpoints were the progression-free survival (PFS) rate and cumulative local recurrence rate (cLRR). Of the 65 primary brain tumor patients registered, 29 glioma patients from eight of 19 PBT facilities met the inclusion criteria. There were 19 glioblastoma patients, eight of other malignant gliomas, and two of low-grade gliomas. For glioblastomas, with a median follow-up period of 16 months, the median survival time was 21.2 months and the OS at 1, 2, 3 and 4 years were 77.4%, 44.9%, 23.9% and 23.9%, respectively. The median PFS period was 10.1 months, the 1, 2, 3 and 4-year PFS were 32.4%, 19.4%, 9.7% and 9.7%, respectively. The 1, 2, 3 and 4-year cLRR were 56.1%, 68.8%, 78.4 and 78.4%, respectively. Grade 3 brain necrosis was observed in two patients. No secondary tumor was observed. This is the first report on the current status of PBT for gliomas in Japan. For glioblastomas, the outcomes of PBT are estimated to be equivalent to historical data of photon therapy. The results of a prospective comparative evaluation of PBT and photon therapy are awaited.

Background Central nervous system (CNS) germ cell tumors account for 15.3% of all CNS tumors in children and adolescents and young adults. Five histologic types and mixed types exist and can be classified into the following clinical risk groups: germinomas, malignant germ cell tumors, and other germ cell tumors. In germinomas, platinum-based chemotherapy and whole ventricle/brain irradiations 23.4 Gy/13 fraction are the standard of care, but late adverse events related to radiation therapy are a problem. In malignant germ cell tumors, chemotherapy with alkylating agents and platinum, craniospinal irradiation (CSI), and local radiation therapy (local dose 50-59.4 Gy/25-33 fractions) have become the standard of care, but the 10-year OS is poor at about 60% and late radiation therapy-related adverse events are an issue. For various reasons, it is not easy to establish a standard of care for mature teratomas and immature teratomas, which constitute the other germ cell tumors, but it is essential to collect knowledge on tumor characteristics and prognosis. Methods and Patients The Japan Children's Cancer Group Brain Tumor Committee has planned a study to validate the classification by histological diagnosis and ancillary tumor markers, a phase III study to test the non-inferiority of radiation dose reduction to standard therapy for germinomas, a phase II study to test the superiority of high-dose chemoradiation with methotrexate intrathecal injection excluding CSI to standard therapy for malignant germ cell tumors, observational studies to elucidate pathogenesis of other germ cell tumors. Discussion If these hypotheses are proven, it is expected to reduce late adverse events and prolong survival with radiotherapy in children and adolescent/young adult generation patients.

Purpose: We retrospectively analyzed the treatment outcomes of Stereotactic irradiation (STI) for large size (2–3 cm) brain metastasis. Materials and methods: One hundred and sixty-nine lesions with 156 patients who underwent STI from January 1, 2013 to December 31, 2015 at 21 institutions participating in the Japanese Radiation Oncology Study Group were included in the study. Patients who had a history of whole-brain irradiation in the past and those who received whole-brain irradiation sequentially with STI were excluded. RANO-BM was used to evaluate the effect on each lesion, and the survival time or time to occurrence of local failure was defined as the number of months from the initial day of STI to the day of the events. Results: The median age was 66 (33–87) years. The median follow-up time was 14 (1–52) months. Male/female = 95/61 cases. The number of brain metastases was 1/2/3/4 or more = 93/35/14/14 cases. The median doses and fraction size were 30 Gy in 3 fractions. The primary site was lung/breast/colon or rectum/others = 95/14/14/33 cases. The median survival time was 16 months. A 1-year overall survival rate was 62% and a 1-year local control rate was 77%. Comparing the 1-year local control rate by the fraction size, single/3 or 4 /5 or more = 66/86/75%, the rate was better in the 3–4 fractions group (Log-rank test, p = 0.069). Cerebral necrosis (Grade 1/2/3/unknown = 9/10/8/3 cases) was observed in 30 lesions (18%), and the median time to diagnosis of brain necrosis was 9 (1–41) months. The incidence of necrosis in the single fraction cases was 29%, which was significantly higher than that in the fractionated irradiation cases (15%) (p = 0.039). Conclusion: Fractionated STI seems to be more favorable than single fraction STI for large brain metastases.

To determine the current practice of stereotactic irradiation (STI) for brain metastases in Japan by a questionnaire survey. A questionnaire was distributed to 313 institutions performing STI with one of the following machines: Gamma Knife (GK), CyberKnife (CK), Novalis (Nov), or other linear accelerator (LINAC)-based systems (OLS). The participation was voluntary. There were 163 responding institutions. The total number of STI treatments between April 2013 and March 2014 was 10,684. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) were performed in 8624 (80.7%) and 2060 (19.3%) cases, respectively. Whole-brain radiation therapy (WBRT) was performed for a total of 3515 cases. For a case model of a 1.5-cm solitary brain metastasis in a non-eloquent area, the most common GTV-PTV margin was 2 mm (22 of 114 institutions), and an institutional standard fraction was 1 (75 of 114 institutions). The doses for the model case also varied from 13.0 to 26.0 Gy (Median 20 Gy) when converted to SRS (α/β = 10). A prescription point was at the PTV margin the most. The median dose constraints which were converted to SRS (α/β = 3) to organs at risk were 12.2, 12.7, and 13.7 Gy for optic nerves, cavernous sinus, and brainstem, respectively. STI for brain metastases in current practice varied significantly among institutions. These different strategies relied mostly on the type of treatment machine used. It is thus necessary to establish a common guideline to express dose prescriptions and plan qualities for different STI machines.

Adenosquamous carcinoma of the pancreas (ASCP) is very rare, comprising only 1–4 % of exocrine malignancies of the pancreas. Several reports have described surgical outcomes for ASCP, but there are few reports of radiotherapy. We treated a case of ASCP with radiotherapy with 50.4 Gy in 28 fractions. The tumor disappeared completely at the end of the radiotherapy but recurred rapidly within the radiation fields, and multiple liver metastases with ascites developed 2 months after treatment, which indicated the possibly high radiosensitivity of the tumor. Initial serum levels of carcinoembryonic antigen, 8.6 ng/mL, and squamous cell-related antigen, 45.8 ng/mL, decreased to within normal limits at the end of radiation therapy, but these 2 tumor markers increased rapidly thereafter.

Object The objective of the present study was to perform a prospective evaluation of the potential efficacy and safety of intraoperative photodynamic therapy (PDT) using talaporfin sodium and irradiation using a 664-nm semiconductor laser in patients with primary malignant parenchymal brain tumors. Methods In 27 patients with suspected newly diagnosed or recurrent primary malignant parenchymal brain tumors, a single intravenous injection of talaporfin sodium (40 mg/m2) was administered 1 day before resection of the neoplasm. The next day after completion of the tumor removal, the residual lesion and/or resection cavity were irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm2 and a radiation energy density of 27 J/cm2. The procedure was performed 22–27 hours after drug administration. The study cohort included 22 patients with a histopathologically confirmed diagnosis of primary malignant parenchymal brain tumor. Thirteen of these neoplasms (59.1%) were newly diagnosed glioblastomas multiforme (GBM). Results Among all 22 patients included in the study cohort, the 12-month overall survival (OS), 6-month progression-free survival (PFS), and 6-month local PFS rates after surgery and PDT were 95.5%, 91%, and 91%, respectively. Among patients with newly diagnosed GBMs, all these parameters were 100%. Side effects on the skin, which could be attributable to the administration of talaporfin sodium, were noted in 7.4% of patients and included rash (2 cases), blister (1 case), and erythema (1 case). Skin photosensitivity test results were relatively mild and fully disappeared within 15 days after administration of photosensitizer in all patients. Conclusions Intraoperative PDT using talaporfin sodium and a semiconductor laser may be considered as a potentially effective and sufficiently safe option for adjuvant management of primary malignant parenchymal brain tumors. The inclusion of intraoperative PDT in a combined treatment strategy may have a positive impact on OS and local tumor control, particularly in patients with newly diagnosed GBMs. Clinical trial registration no.: JMA-IIA00026 (https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=862).

Purpose To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. Methods and Materials We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women's Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. Results The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. Conclusion These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

A 54-year-old woman presented with hematopyuria. She had experienced difficulty in urinating since undergoing surgery for rectal cancer 15 years earlier. Cystoscopy revealed an edematous mucosa and a submucosal tumor. Computed tomography showed irregular thickening of the bladder wall and tumor-like masses. Although she started clean intermittent self-catheterization to manage the neurogenic bladder, the thickening of the wall became worse. We performed transurethral biopsy of the bladder, and histopathological examination of the specimens revealed non-Hodgkin’s lymphoma of the mucosa-associated lymphoid tissue (MALT) type. A diagnosis of stage IE primary MALT lymphoma of the bladder was made. The tumor persisted even after antibiotic therapies for a urinary tract infection and eradication of Helicobacter pylori. Definitive radiotherapy (30 Gy) was administered to the bladder. Subsequent computed tomography revealed disappearance of the wall thickening, and transurethral resection showed no residual lesion of lymphoma. She has maintained a complete response for 9 months of follow-up.

Trilateral retinoblastoma (TRb) is an intracranial neurogenic tumor associated with unilateral or bilateral retinoblastoma and has very poor prognosis. Patients typically die from leptomeningeal tumor dissemination.A 3-year-old girl who had been diagnosed with TRb had a disseminated relapse after a tumorectomy, cerebrospinal irradiation, and conventional chemotherapy. The disseminated tumor disappeared after the first autologous peripheral blood stem cell transplantation (PBSCT) with high-dose melphalan and thiotepa. During the second complete remission, a second autologous PBSCT with high-dose busulfan and melphalan was performed. Seven months after the first PBSCT, the second relapse occurred, and we subsequently performed an allogeneic PBSCT with myeloablative chemotherapy consisting of melphalan, thiotepa, and cyclophosphamide. The patient showed clinical improvement after the allogeneic PBSCT.Although high-dose chemotherapies have a curative effect for some patients with TRb, the prognoses of disseminated tumors are still poor. Further examination of the high-dose chemotherapy is necessary for the time, the conditioning drugs, and the hematopoietic stem cell sources.

Breast cancer/Anxiety/Chromogranin A/State-Trait Anxiety Inventory (STAI)/Radiation. We conducted a prospective study to assess the a nxiety and salivary Chromogranin A (CgA), which is considered to be a biomarker of the stress response, in outpatients receiving breast conserving surgery followed by radiation therapy (RT) to the whole breast. Fifty consecutive patients who received wholebreast RT were enrolled in this study. The anxiety levels were measured by the State-Trait Anxiety Inventory (STAI) at the beginning of RT (baseline), 30 Gy, completion of RT, and 1 and 3 months after RT. Salivary CgA levels were also measured at the same time. The mean state anxiety score for all patients was 46.16 with a standard error (SE) of 1.57 at the beginning of RT (baseline) which continued to decline during and after RT. It reached its lowest score with 36.34 ± 1.56 at 3 months after RT (p < 0.0001). The mean trait anxiety score for all patients was 43.10 ± 1.54 at baseline and remained constant during RT but began to decline after completion of RT and reached a low level at 3 months after RT (p = 0.0021). The mean salivary CgA concentration for all patients demonstrated no consistent trends over time, but at 30 Gy the concentration showed a significant decreasing pattern (p = 0.0473). Salivary CgA concentrations and state anxiety and trait anxiety scores at all time points showed no correlation. The mean anxiety scores measured by STAI showed no positive correlation with s alivary CgA concentration for breast cancer patients undergoing radiation therapy following breast conserving surgery.

1993年1月から2005年8月に当科で根治的放射線治療が施行された中咽頭癌IVA-B期患者57例を対象として治療成績の検討を行った。年齢は34～84歳（中央値62歳），性別は男性43例，女性14例であり，発生部位は前壁16例，側壁39例，後壁1例，上壁1例であった。全身化学療法が49例で施行されたが，導入化学療法（induction chemotherapy: ICT）：25例，ICT+同時併用化学放射線療法（concurrent chemoradiotherapy: CCRT）：15例，CCRT：9例であった。37例に1.2Gy1日2回の多分割照射法で60～82Gy（中央値72Gy），20例には通常分割照射法で60～72Gy（中央値66Gy）の放射線治療が施行された。初期治療として放射線治療後の救済手術が5例に施行された。5年粗生存率，無病生存率はそれぞれ52.9%，51.4%であった。T3以上，N2c以上，高分化型であった症例で有意に予後不良であった。しかし，全身化学療法の有無，施行時期，照射スケジュールには生存率に有意を認めなかった。未だ治療成績は良好とは言えず，さらなる治療成績改善のための検討が必要と考えられた。

BACKGROUND: Standard therapeutics for glioblastoma is tumor removal followed by radiotherapy and chemotherapy with temozolomide (TMZ). Additional six cycles of TMZ is usually given, but it is unclear whether six cycles is sufficient to reduce recurrence. In our series, 25% of patients with GBM treated with TMZ lived more than one year without recurrence, and most of them received 12 cycles or more of TMZ chemotherapy. We retrospectively assessed the efficacy of long term TMZ in these case series. METHODS: Patients with newly diagnosed GBM, treated with 12 cycles or more TMZ after concomitant radiotherapy without relapse, were consecutively sampled at our institution from 2006 to 2014. The patents were categorized into 4 groups according to number of TMZ chemotherapy A) 12 cycles, B) 24 cycles, C) more than 24 cycles until relapse, D) beyond 12 cycles (included B, C). Progression free survival (PFS) after initial surgery, and PFS after the date of the final chemotherapy were analyzed by Kaplan-Meier estimate. RESULTS: A total of 52 patients met the criteria. Groups A, B, C and D included 12, 14, 12 and 40 patients, respectively. Each group had similar backgrounds. Median survival time (MST) and PFS of all patients was 6.8 and 4.3 years, respectively. There were no significant differences in PFS after the initial surgery between group A and B (p = 0.5889) and between C and D (p = 0.9243). Also, PFS after the final date of chemotherapy between group A and D (p = 0.5778), C and D (p = 0.8498) showed no difference, suggesting no benefit of more than 12 cycles of chemotherapy. CONCLUSION: This study suggested that patients with newly diagnosed GBM who are able to continue 12 cycles of TMZ chemotherapy can expect 6.3 years of OS and 4.3 years of PFS. More than 12 cycles of chemotherapy showed no additional survival benefit.

Purpose: The aims of this study were twofold: ( 1 ) to examine the effects of dual inhibition of 2 members of the HER family, the epidermoid growth factor receptor (EGFR) and HER2/ neu , by gefitinib (ZD1839) and trastuzumab on radiosensitivity; and ( 2 ) to explore the molecular mechanism of radiosensitization especially focusing on the survival signal transduction pathways by using A431 human vulvar squamous carcinoma cells expressing EGFR and HER2/ neu . Methods and Materials: The effects of inhibitors on the radiation-induced activation of EGFR and/or HER2/ neu , and the intracellular proteins that are involved in their downstream signaling, were quantified by the Western blot. Radiosensitizing effects by the blockage of EGFR and/or HER2/ neu were determined by a clonogenic assay. Results: Radiation-induced activation of the EGFR and HER2/ neu was inhibited with ZD1839 and/or trastuzumab. ZD1839 also inhibited the radiation-induced phosphorylation of HER2/ neu . Radiation in combination with the HER family inhibitors inhibited the activation of Akt and MEK1/2, the downstream survival signaling of the HER family. ZD1839 enhanced radiosensitivity with a dose-modifying factor (DMF) (SF3) of 1.45 and trastuzumab did so with a DMF (SF3) of 1.11. Simultaneous blockade of EGFR and HER2/ neu induced a synergistic radiosensitizing effect with a DMF (SF3) of 2.29. Conclusions: The present data suggest that a dual EGFR and HER2/ neu targeting may have potential for radiosensitization in tumors in which both of these pathways are active.

Objective: To determine the average national practice of postoperative radiotherapy for uterine cervical cancer in Japan. Methods: The Japanese Patterns of Care Study (PCS) reviewed the process of care employed for 455 uterine cervical cancer patients who were treated with surgery followed by postoperative radiotherapy (RT) during 1995–1997. Cases with missing data were excluded from calculations of percentage and significance for each of the surveyed items. Results: According to FIGO stages, 198 patients (45%) were in stage I, 52 patients (12%) were in stage IIA, 146 patients (33%) were in stage IIB and 46 patients (10%) were in stage III/IVA. The most common surgical procedure among the patients was radical hysterectomy (73%). Three hundred and seventy patients (82%) were treated with external beam RT (ERT) alone, and 74 patients (17%) were treated with a combination of ERT and intracavitary RT (ICRT). A midline block was used for the pelvic field in 63 patients (14%). Only seven patients (2%) were treated with extended field ERT. Pelvic ERT was most often performed using AP-PA opposed fields for 431 patients (97%). A majority of the patients (312 patients, 70%) were treated with a total dose of 45.0–50.4 Gy for ERT. Chemotherapy (CT) was administered to 178 patients (40%), neoadjuvant preoperative CT was administered to 80 patients (22%) and concurrent CT with postoperative RT was administered to 29 patients (8%). Conclusion: This PCS established the national practice average of postoperative RT for uterine cervical cancer. Follow-up studies need to be conducted to determine whether the observed differences in treatment processes affect outcomes.

Docetaxel has shown remarkable radiosensitizing propertiesin vitro. In this study we investigated whether the addition of docetaxel to radiotherapy enhanced tumor response in patients with advanced or recurrent breast cancer. A total of 35 patients were enrolled in this study. Docetaxel was administered concurrently during radiotherapy. Radiation doses were 54 to 69 Gy (median 60 Gy). In those enrolled through January 2000, docetaxel 40 mg/m2 was administered biweekly (once every two weeks), with subsequent dose adjustments based on tolerance and bone marrow and liver function. Beginning in February 2000, a weekly docetaxel schedule was used instead. This new regimen was based on data suggesting reduced myelosuppression with this regimen. The weekly dose rate was 20 mg/m2, with dose reductions for impaired organ function. All patients were evaluated for toxicity and response and a total of 40 irradiated sites were evaluated for local response. The overall response rate of irradiated sites was 95% and the CR rate was 68%. CR and PR were achieved in 40%, 37% of patients, respectively. Acute toxicities were tolerated by most patients: 17% had Grade 3-4 neutropenia, 6% had Grade 3-4 radiation dermatitis, and 3% had Grade 3-4 pneumonitis. The combination of docetaxel with radiotherapy is an active and safe regimen in patients with inoperable advanced or recurrent breast cancer. We determined the recommended dose of docetaxel with concomitant radiotherpy to be 20 mg/m2 weekly for a Phase II study. Further study is necessary to assess the impact of this treatment on long-term outcome.

142 Background: Low-dose-rate brachytherapy (BT) is the internal radiation therapy for non-metastatic prostate cancer by implanting radioactive isotope Iodine 125 into the prostate. The carcinogenetic effect of radiation for the treatment of cancer has been proven during the last decades. However, few studies have been reported about brachytherapy-induced secondary malignancies. In this study, we assessed the BT-induced secondary malignancies in our institution. Methods: We reviewed 487 patients treated with low-dose-rate BT from 2006 to 2016 in our hospital. We checked the occurrence of metachronous malignancies (MM) in all the patients and examined the features of MM including the number, organ sites, histology, period from BT to the occurrence, and analyzed whether the features meet the criteria of radiation-induced malignancies. We also examined the relationship between the BT-related radiation doses and the occurrence of MM. We adopted the criteria of radiation-induced cancer proposed by Sakai et al in 1981; different pathological feature from the organ of origin, the follow-up duration after radiation therapy (over 5 years), and whether the lesion is located in the irradiated field. Results: After a median follow-up period of 57 months (range 10-125 months), 23 MM occurred, which were bladder cancer in 4 cases (0.8%), esophageal in 2 (0.4%), gastric in 5 (1.0%), colon in 4 (0.8%), rectal in 3 (0.6%), pancreatic in 1 (0.2%), lung in 3 (0.6%), and brain in 1 (0.2%). Time from initial treatment to MM was 36 months (range 1-85 months). None of the cases had experienced biochemical recurrence. Average radiation dose to the urethra and the rectum including UD90, UD5, U200, R100, R150 showed no significant difference compared to the patients without occurrence of MM. According to the Sakai’s criteria, one bladder and one rectal cancer were judged as radiation-induced secondary malignancies (0.2%). Conclusions: The risk of secondary malignancies in patients undergoing BT was very low. Further studies with longer follow-up are required because it has been only about 10 years since low-dose-rate brachytherapy started in Japan.

OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection.

Background. Kaposi's sarcoma is frequently found in association with acquired immunodeficiency syndrome (AIDS). We report on radiotherapy for patients with AIDS-related Kaposi's sarcoma at Tokyo Metropolitan Komagome Hospital.

Purpose: In order to investigate the role of potentially lethal damage repair (PLDR) in cellular radiosensitivity, PLDR and its inhibitory effect by caffeine was examined. In addition, cell cycle distribution was also examined. Materials and methods: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, with different radiosensitivities in vitro were used. The capacity for PLDR was examined using confluent-phase cells, and evaluated by calculating the recovery ratio. Inhibitory effect of caffeine on PLDR was examined with doses of 1, 5 and 10 mM. Results: The capacity of PLDR in two cell lines reflected radiosensitivity. The recovery ratio after irradiation of 5 Gy was 2.8 in the radiosensitive NMT-1 and 5.2 in the radioresistant NMT-1R, and recovery reached its peak level at 6 h in both cell lines. The degree of inhibition of PLDR was weaker in NMT-1R than that in NMT-1 at the same dose level, and was correlated with reduction of G2-arrested cells by caffeine. Conclusions: The results of this study suggest that the capacity of PLDR may be one of the determinant factors for radiosensitivity in the two cell lines used, and the inhibitory effect of caffeine on PLDR was in part attributable to the modification of the cell cycle progression.

The differences between two rat yolk sac tumor cell lines, which are of the same origin but differ in their response to irradiation, in thermal sensitivity and development of thermotolerance were investigated. A radiosensitive cell line NMT-1 is consistently less heat sensitive than the radioresistant cell line NMT-1R. The thermotolerances in NMT-1 and in NMT-1R preheated at 43 degrees C for 30 min, respectively, reached peaks at 6 h and at 12 h, but did not completely disappear at 48 h. Thermotolerance with a good correlation between both cell lines with HSP70 accumulation was observed in a different time course after a primary heating.

Purpose: We reported that two established rat yolk sac tumor cell lines differ in their radiosensitivity by 1.7 fold, and the variation is most likely manifested by the differences seen in their apoptotic response. We investigated the relationship between radiosensitivity and p53 in these cell lines. Methods and Materials: We assessed the status of p53 in cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequence analysis, and also analyzed protein expression of p53, p21, and bax as a function of time after irradiation to determine the signal transduction for p53 by immunoblotting. Results: A band shift was observed only in exon 7 for the radioresistant NMT-1R cells and no band shift was detected for the radiosensitive NMT-1 cells. A band shift was confirmed also at the mRNA level. Exon 7 of p53 DNA showed a three base substitution of DNA at codon 267 to 268. Expression of p53, p21, and bax proteins in NMT-1R cells did not change after 10 Gy irradiation; however, in NMT-1 cells, the expression of these proteins was increased from 1–12 h after irradiation. Conclusion: A loss of p53 function by radiation-induced mutation of p53 decreased the radiosensitivity in these cell lines.

近年, 画像診断の進歩ならびに悪性腫瘍に対する治療成績の向上に伴い, 重複癌の頻度が急速に増加してきており, 重複癌に関して種々の組み合わせの報告が数多くされている.しかし, 現在までのところ子宮頸癌と腎細胞癌の重複癌に関する報告はあまりみられていない.今回, 子宮頸癌の放射線治療経過中に画像診断にて腎細胞癌が偶然発見され, 3年間にわたり経過を観察しえた症例を経験した.本症例は放射線治療が不完全な状態で終了したため, 子宮頸癌の局所再発により初回治療から3年1か月後に尿路障害にて死亡したが, 経過中に腎細胞癌の明らかな増大は認められなかった.剖検にて子宮頸癌と腎細胞癌の重複癌であることが確認された.

The prognostic factors and the correlation between local control and total dose were investigated for the patients with invasive thymoma treated by a combination of radiation therapy and surgery or radiation therapy alone. Eighteen patients were retrospectively analyzed. Our treatment strategy was to give the target volume a total dose of at least 50 Gy for patients with microscopic residual and 60 Gy or more for macroscopic residual. The actuarial survival rates were 61 % at 5 years and 54 % at 10 years in all patients. All patients having a complete resection survived disease-free for more than 6 years while the survival rates of patients with macroscopic residual or unresected tumors were 38 % at 5 years and 25 % at 10 years (p

The objective of the present study was to perform a prospective evaluation of the potential efficacy and safety of intraoperative photodynamic therapy (PDT) using talaporfin sodium and irradiation using a 664-nm semiconductor laser in patients with primary malignant parenchymal brain tumors.In 27 patients with suspected newly diagnosed or recurrent primary malignant parenchymal brain tumors, a single intravenous injection of talaporfin sodium (40 mg/m(2)) was administered 1 day before resection of the neoplasm. The next day after completion of the tumor removal, the residual lesion and/or resection cavity were irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm(2) and a radiation energy density of 27 J/cm(2). The procedure was performed 22-27 hours after drug administration. The study cohort included 22 patients with a histopathologically confirmed diagnosis of primary malignant parenchymal brain tumor. Thirteen of these neoplasms (59.1%) were newly diagnosed glioblastomas multiforme (GBM).Among all 22 patients included in the study cohort, the 12-month overall survival (OS), 6-month progression-free survival (PFS), and 6-month local PFS rates after surgery and PDT were 95.5%, 91%, and 91%, respectively. Among patients with newly diagnosed GBMs, all these parameters were 100%. Side effects on the skin, which could be attributable to the administration of talaporfin sodium, were noted in 7.4% of patients and included rash (2 cases), blister (1 case), and erythema (1 case). Skin photosensitivity test results were relatively mild and fully disappeared within 15 days after administration of photosensitizer in all patients.Intraoperative PDT using talaporfin sodium and a semiconductor laser may be considered as a potentially effective and sufficiently safe option for adjuvant management of primary malignant parenchymal brain tumors. The inclusion of intraoperative PDT in a combined treatment strategy may have a positive impact on OS and local tumor control, particularly in patients with newly diagnosed GBMs. Clinical trial registration no.: JMA-IIA00026 (https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=862).

The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and

‘Dropped head syndrome’ (DHS) is characterized by severe weakness of the muscles of the back of the neck, resulting in chin-on-chest deformity. Dropped head syndrome induced by radiotherapy is very rare. We report a case of DHS following chemoradiotherapy with a total of 64.8 Gy in 36 fractions for nasopharyngeal carcinoma.

Malignant peritoneal mesothelioma is extremely rare, and its prognosis is poor. The median survival period is said to be approximately one year after diagnosis. We report a case of recurrent malignant peritoneal mesothelioma treated with concurrent chemoradiotherapy (CCRT). The patient has been alive for six years without recurrence. This report seems to be the first that indicates CCRT to be useful for peritoneal mesothelioma. The patient was a 21-year-old woman who underwent emergency surgery of the in acute abdomen at another hospital. The resected tumor was 18 cm in size and pathological examination revealed that it was a malignant mesothelioma of the epithelioid type. CAP therapy (cyclophosphamide+adriamycine+cisplatin)+CPT-11 administration was given only one course, and the patient was then transferred to our hospital. She underwent resection of the residual disease and six courses of TC therapy (paclitaxel+carboplatin) as adjuvant chemotherapy. Twelve months after chemotherapy, pelvic recurrence occurred. We attempted surgery but only biopsy could be performed because of a pelvic wall invasion. The patient underwent CCRT with weekly cisplatin. The tumor was reduced by irradiation of 50. 4 Gy and disappeared after 6 months. No recurrence has been found six years since the last treatment. CCRT might be effective against malignant peritoneal mesothelioma of the epithelioid type.

We performed double high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) in 3 children with medulloblastoma and primary leptomeningial dissemination, including spinal metastasis. After resection of the main tumor mass, 30.6 Gy whole craniospinal radiation therapy and 4 or 5 courses of conventional chemotherapy with vincristine (1.5 mg/m), carboplatin (560 mg/m), ifosfamide (9000 mg/m), and etoposide (500 mg/m), and 2 courses of high-dose thiotepa (680 mg/m) and melphalan (240 mg/m) therapy with PBSCT were administered. Two patients with low erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene expression achieved long-term survival (41 mo and 40 mo) but the patient with high ERBB2 expression relapsed 9 months after the second PBSCT.

The aim of this study was to evaluate the impact of dysadherin and E-cadherin expression on the clinical outcomes, including the treatment outcomes and recurrence pattern, in patients with head and neck cancer.Tumor specimens were obtained from 48 head and neck cancer patients who were treated by radiation therapy and the specimens were immunohistochemically stained for dysadherin and E-cadherin. The expressions were graded according to the percentage area occupied by cancer cells showing positive staining for E-cadherin and dysadherin as follows: grade 0, less than 10%; grade 1, 10-50%; grade 2, more than 50%. The correlations between the expression of E-cadherin and dysadherin and the clinical outcomes, including the treatment outcomes and recurrence pattern, were analyzed.The complete response (CR) rate in the patients with a dysadherin expression grade of 0 or 1 was 70% and that in the patients with dysadherin expression grade of 2 was 38%; the difference was significant (p0.05). Regarding the pattern of recurrence, the expression grade of dysadherin or E-cadherin alone was not correlated with the recurrence pattern; however, patients with a difference in the expression grade between dysadherin and E-cadherin (Dys-Ecad value) of 1 or 2 showed a significantly higher rate of lymph node and/or distant metastasis (55%) as compared with those with a Dys-Ecad value of1 (22%) (p0.05).Dysadherin and E-cadherin expression might serve as useful prognostic factors in patients with head and neck cancer treated by definitive radiation therapy.

Radiotherapy plays an important role in the management of cancer patients, and half of the patients with malignant tumors are treated with radiotherapy in the United States. In Japan, the necessity of radiation therapy has come to be widely acknowledged in cancer treatment, and more and more cancer patients are being treated with radiation. External beam radiation is the most-used radiotherapy at the present time. The advantage is that this treatment modality can be used in a short time, although the problem is that not only the cancer lesion but also the surrounding normal tissue is irradiated,causing an adverse effect on normal tissue. In order to solve this problem,treatments such as 3D-Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT), Stereotactic Radiation Surgery (SRS) and Stereotactic Radiation Therapy (SRT) are clinically used as an extremely precise radiotherapy, thanks to the advances in computer technology in recent years. Therefore, the purpose of these extremely precise radiation therapies is to administer a high dose to the tumor intensively, and to suppress quantities of magnetism to normal tissues. IMRT treatment results for prostate cancer patients and head and neck cancer patients are reportedly better than with other irradiation methods. In this chapter,we explain the external irradiation method with the focus on IMRT and the extremely precise radiotherapy preformed in the Tokyo Women's Medical University Hospital.

Radiotherapy is considered to be associated with psychological distress. We assessed the mental status, anxiety, and the factors associated with these in cancer patients about to receive radiotherapy.Hospitalized patients about to receive radiotherapy participated. Psychological status was assessed by a psychiatrist, based on interview about the type of anxiety related to cancer or radiotherapy as well as self-rating questionnaires.Eligible data were collected from 94 patients. The incidence of mental disorders was 20%. The total mood disturbance scores were significantly higher in patients with poor performance status. The most common type of anxiety regarding radiotherapy was acute adverse effect, and the predictors were palliative treatment and living alone.Mental disorders, mood disturbance, and anxiety in patients cannot be neglected in radiation oncology practice. Especially careful attention should be paid to patients with these predictive factors.

Objective The aim of this study is to establish Japanese national practice patterns for uterine cervical cancer patients who received radiotherapy without surgery. Methods The Japanese Patterns of Care Study (JPCS) conducted a national survey of 73 institutions using two-stage cluster sampling, and collected specific information on 591 patients with uterine cervical cancer treated by radiotherapy without planned surgery between 1995 and 1997. Results The median age of the patients was 70 years. Karnofsky performance status (KPS) was >/=90 for 37%. Most patients (95%) had histology of squamous cell carcinoma. Ten percent were stage I, 29% stage II, 48% stage III and 13% stage IVA. Photon beams of 10-14 MV were the most used for external beam radiotherapy (EBRT). The beam energy utilized varied significantly by institution strata. Midline block was used in approximately 70% of institutions. Intracavitary brachytherapy (ICBT) was performed in 77%. Institution strata correlated significantly with the ICBT application. The majority of patients (89%) were treated with high-dose-rate (HDR) ICBT. The median single point A dose of HDR-ICBT was 600 cGy. The median summated point A dose from EBRT and HDR-ICBT was 5800 cGy (range: 1196-8600). The median overall treatment time including ICBT was 49 days. Twenty-four percent of the patients received chemotherapy. Concurrent chemoradiation was performed in 5%. Conclusions The JPCS established the Japanese national practice patterns of care for uterine cervical cancer patients treated with radiotherapy without planned surgery between 1995 and 1997. This survey demonstrated that the institutional strata significantly affected several practice patterns.

The aim of this study was to improve tumor control, the survival rate and organ preservation for locally advanced head and neck cancer by using induction chemotherapy followed by hyperfractionated radiotherapy and concurrent chemotherapy.Thirty-five patients with stage III-IVB head and neck cancer were treated with this protocol. Induction chemotherapy consisted of cisplatin and fluorouracil and concurrent chemotherapy consisted of carboplatin and doxifluridin. Radiotherapy was administered twice a day until a dose of 72 Gy was reached.Twenty-two (63%) and 13 patients (37%) achieved complete responses and partial responses, respectively. In terms of non-hematological toxicities, grade 3 mucositis was observed in 49% of the patients. The overall 5-year survival was 53.5% and the progression-free survival was 40.6%.Response to induction chemotherapy was useful as a predictive factor for ultimate outcome and organ conservation. More intensive regimen or other combination chemotherapy is needed to improve treatment outcome with hyperfractionated radiotherapy.

We report a case of recurrent breast cancer with chronic renal failure in a 58-year-old female. She could be treated on an outpatient basis under good general condition for most of her remaining life by chemoradiotherapy in combination with hemodialysis. Modification of the chemoradiotherapy procedures and collaboration of medical staff including the doctor in charge of home medical care and her family was indispensable in keeping her hospital stay as short as possible.

To investigate cell killing by means of low dose-rate irradiation (LDRI) combined with concurrent mild hyperthermia and to determine the effect of low-dose caffeine on this combination treatment.Human lung adenocarcinoma cells, LK87, were treated with LDRI (50 cGy/h) in combination with mild hyperthermia at 41 degrees C and low-dose caffeine (1 mM). Cell survival was estimated by clonogenic assay. Flow-cytometry was performed with PI staining using FACScan. Heat-shock protein (HSP72/73) was measured by the Western blotting method. All treatments were simultaneously performed for up to 48 h (24 Gy).LDRI cytotoxicities were enhanced by hyperthermia at 41 degrees C. D0 calculated from the dose-response curve for LDRI combined with 41 degrees C was 3.46 Gy whereas it was 6.55 Gy for LDRI alone. The survival curve for LDRI +41 degrees C demonstrated no chronic thermotolerance up to 48 h. For LDRI + simultaneous low-dose caffeine, cell killing was also enhanced, where D0 was 3.38 Gy at 37 degrees C. Radiosensitization caused by caffeine was enhanced by combination with simultaneous mild hyperthermia at 41 degrees C, where D0=1.78 Gy. Cell cycle analysis demonstrated remarkable G2 and mild G1 arrest for LDRI alone, but only G1 arrest was observed for LDRI combined with 41 degrees C and for LDRI combined with caffeine. Strong and early G1 arrest was observed in the treatment with LDRI + caffeine at 41 degrees C. The amount of HSP72/73 in the combination of LDRI with caffeine at 41 degrees C was less than that at 41 degrees C alone.LDRI cytotoxicity was enhanced by non-lethal hyperthermia. Low dose caffeine produced further cell killing in the combination of LDRI with mild hyperthermia.

Primary malignant lymphoma of the uterine body is extremely rare. There are few reports concerning magnetic resonance images (MR) of uterine body lymphoma although there are several reports concerning uterine cervical lymphoma. The MR images of a 66-year-old woman with primary malignant lymphoma of the uterine body showed that the myometrium was diffusely involved, exhibiting an almost homogeneous character, and the normal zonal anatomy of the uterine cervix was preserved, with the endometrium being partly recognized near the center of the tumor. We report suggestive findings on MR images of primary malignant lymphoma of the uterine body.

BACKGROUND It has been suggested that the p53 tumor suppressor gene regulates the radiosensitivity in human malignancies after irradiation; however, in cervical carcinoma, the role of the p53 gene is still unclear because of inactivation of functional p53 by infection with human papillomavirus (HPV). The objective of this study was to clarify the effects of p53 status and HPV infection on the clinical outcome of patients with cervical carcinoma after undergoing radiation therapy. METHODS Fifty-two patients with International Federation of Gynecology and Obstetrics Stage IIIB squamous cell carcinoma of the cervix who received radiation therapy alone were reviewed. The combination of external beam irradiation therapy and three sessions of intracavity brachytherapy irradiation was performed for all patients. Genomic DNA extracted from paraffin embedded tissues was examined for HPV types 16, 18 and 33 by the polymerase chain reaction (PCR) method and for p53 status by PCR-single-strand conformation polymorphism (PCR-SSCP) technique. The effects of HPV infection, p53 status, and other parameters on clinical outcome were investigated by univariate analysis. RESULTS HPV-DNA was detected in 40 patients (76.9%), and 14 patients (26.9%) had mutations of the p53 gene in the study. There was a significant correlation between the existence of HPV and p53 status (P < 0.001). Mutations of the p53 gene were detected in 6 of 12 patients (50%) who had local recurrent tumors, whereas p53 were wild type in 32 of 40 patients (80%) who achieved local control. The p53 mutation had a significant correlations with local tumor recurrence. Furthermore, p53 status caused statistical significant differences in the curves of the recurrence free survival rate and local control rate as determined by the log rank test (P = 0.02 and P = 0.03, respectively). Conversely, no obvious correlation with any clinical outcome for patients with cervical carcinoma was found concerning HPV infection. CONCLUSIONS It is possible that the p53 gene may be used as a predictive factor in radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix. Cancer 2001;91:80–9. © 2001 American Cancer Society.

The radiosensitizing effects of caffeine on two rat yolk sac tumor cell lines with a different p53 status were investigated. A reduction of radiation-induced G 2 arrest was caused by caffeine at a concentration of 2 mM in both cell lines. The reduction of survival was observed in a combination of radiation and 2 mM caffeine only in a lower radiation dose range, but not in a higher dose range in NMT-1 with a wild type p53. Radiosensitization of caffeine was recognized even in a higher dose range for cells with a mutant-type p53. Apoptosis, which was not prominent after irradiation alone or caffeine treatment alone, was induced by irradiation in combination with caffeine in cells with a mutant-type p53 through a p53-independent pathway.