Takashi Uno

Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

PURPOSEnTo evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML).nnnMETHODS AND MATERIALSnEighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone.nnnRESULTSnThe median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037).nnnCONCLUSIONSnThe majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

Coronal reformatted CT images contribute to the precise evaluation of the radiofrequency ablative margin for hepatocellular carcinoma

ObjectiveThe purpose of the present study was to evaluate the usefulness of coronal reformatted images obtained from 64-slice multi-detector computed tomography to assess the ablative margin (AM) in hepatocellular carcinoma (HCC) treated with radio frequency ablation (RFA).MethodsNinety-five HCC nodules were analyzed in 66 HCC patients treated with RFA. Two radiologists and one hepatologist independently reviewed axial CT images with or without coronal reformatted images in HCC treated with RFA. Nodules were determined as AM-sufficient (≥5xa0mm) or AM-insufficient (<5xa0mm). The level of interobserver agreement was measured using the weighted kappa test. The sensitivity, specificity, and positive and negative predictive values (NPVs) of an insufficient AM (<5xa0mm) to predict local recurrence were evaluated.ResultsThe numbers of AM-sufficient nodules judged by readers 1–3 based on axial images and both axial and coronal images were 56, 49, and 58, and 47, 33, and 48, respectively. Excellent agreement and good to excellent agreement were obtained among the three readers on axial image readings and both axial and coronal image readings, respectively. The mean sensitivity, specificity, and positive and NPVs of an insufficient AM on axial images and both axial and coronal images to predict local recurrence were 64%, 60%, 17%, and 93%, and 95%, 50%, 20%, and 97%, respectively.ConclusionsCoronal reformatted CT images should be utilized to evaluate the AM in HCC treated with RFA in order to decrease the risk of local recurrence following treatment.

Initial experience of radiotherapy plus cetuximab for Japanese head and neck cancer patients

In Japan, cetuximab with concurrent bioradiotherapy (BRT) for squamous cell carcinoma of head and neck (SCCHN) was approved in December 2012. We herein report our initial experience of BRT, with special emphasis on acute toxicities of this combination therapy. Thirty-one non-metastatic SCCHN patients who underwent BRT using cetuximab between July 2013 and June 2014 were retrospectively evaluated. All patients received cetuximab with a loading dose of 400 mg/m2 one week before the start of radiotherapy, followed by 250 mg/m2 per week during radiotherapy. The median cycle of cetuximab was seven cycles and the median dose of radiotherapy was 70 Gy. Twenty-five patients (80.6%) accomplished planned radiotherapy and six cycles or more cetuximab administration. Six patients (19.4%) discontinued cetuximab. Grade 3 dermatitis, mucositis and infusion reaction occurred in 19.4%, 48.3% and 3.2%, respectively. One patient experienced Grade 3 gastrointestinal bleeding caused by diverticular hemorrhage during BRT. Grade 3 drug-induced pneumonitis occurred in two patients. The response rate was 74%, including 55% with a complete response. BRT using cetuximab for Japanese patients with SCCHN was feasible as an alternative for cisplatin-based concurrent chemoradiation, although longer follow-up is necessary to evaluate late toxicities.

Delayed renal dysfunction after total body irradiation in pediatric malignancies

The purpose of this study was to retrospectively evaluate the incidence of delayed renal dysfunction after total body irradiation (TBI) in long-term survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and 2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for HSCT at Chiba University Hospital. Nine patients who survived for more than 5 years were enrolled in this study. No patient had any evidence of renal dysfunction prior to the transplant according to their baseline creatinine levels. The median age at the time of diagnosis was 6 years old (range: 1–17 years old). The follow-up period ranged from 79–170 months (median: 140 months). Renal dysfunction was assessed using the estimated glomerular filtration rate (eGFR). The TBI dose ranged from 8–12 Gy delivered in 3–6 fractions over 2–3 d. The patients were treated with linear accelerators in the supine position, and the radiation was delivered to isocentric right–left and left–right fields via the extended distance technique. The kidneys and the liver were not shielded except in one patient with a left adrenal neuroblastoma. No patient required hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The remaining patients did not demonstrate any eGFR deterioration. Only one patient developed hypertension. By evaluating the changes in eGFR, renal dysfunction among long-term survivors of TBI/HSCT could be detected. Our results suggested that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects renal function.

Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

BackgroundThere have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma.MethodsThe retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5xa0months (range: 3.7-124.6xa0months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population.ResultsThere were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma.ConclusionThere was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma, especially of diffuse large B-cell lymphoma.

Japanese Structure Survey of High-precision Radiotherapy in 2012 Based on Institutional Questionnaire about the Patterns of Care

OBJECTIVEnThe purpose of this study was to clarify operational situations, treatment planning and processes, quality assurance and quality control with relevance to stereotactic radiotherapy, intensity-modulated radiotherapy and image-guided radiotherapy in Japan.nnnMETHODSnWe adopted 109 items as the quality indicators of high-precision radiotherapy to prepare a questionnaire. In April 2012, we started to publicly open the questionnaire on the website, requesting every institution with radiotherapy machines for response. The response ratio was 62.1% (490 out of 789 institutions responded).nnnRESULTSnTwo or more radiotherapy technologists per linear accelerator managed linear accelerator operation in ∼90% of the responded institutions while medical physicists/radiotherapy quality managers were engaged in the operation in only 64.9% of the institutions. Radiotherapy certified nurses also worked in only 18.4% of the institutions. The ratios of the institutions equipped for stereotactic radiotherapy of lung tumor, intensity-modulated radiotherapy and image-guided radiotherapy were 43.3, 32.6 and 46.8%, respectively. In intensity-modulated radiotherapy planning, radiation oncologists were usually responsible for delineation while medical physicists/radiotherapy quality managers or radiotherapy technologists set up beam in 33.3% of the institutions. The median time required for quality assurance of intensity-modulated radiotherapy at any site of brain, head and neck and prostate was 4 h. Intensity-modulated radiotherapy quality assurance activity had to be started after clinical hours in >60% of the institutions.nnnCONCLUSIONSnThis study clarified one major issue in the current high-precision radiotherapy in Japan. A manpower shortage should be corrected for high-precision radiotherapy, especially in the area relevant to quality assurance/quality control.

Patterns of radiotherapy practice for biliary tract cancer in Japan: results of the Japanese radiation oncology study group (JROSG) survey

BackgroundThe patterns of radiotherapy (RT) practice for biliary tract cancer (BTC) in Japan are not clearly established.MethodsA questionnaire-based national survey of RT used for BTC treatment between 2000 and 2011 was conducted by the Japanese Radiation Oncology Study Group. Detailed information was collected for 555 patients from 31 radiation oncology institutions.ResultsThe median age of the patients was 69xa0years old (range, 33–90) and 81% had a good performance status (0–1). Regarding RT treatment, 78% of the patients were treated with external beam RT (EBRT) alone, 17% received intraluminal brachytherapy, and 5% were treated with intraoperative RT. There was no significant difference in the choice of treatment modality among the BTC subsites. Many patients with EBRT were treated with a total dose of 50 or 50.4xa0Gy (~40%) and only 13% received a total dose ≥60xa0Gy, even though most institutions (90%) were using CT-based treatment planning. The treatment field consisted of the primary tumor (bed) only in 75% of the patients. Chemotherapy was used for 260 patients (47%) and was most often administered during RT (64%, 167/260), followed by after RT (63%, 163/260). Gemcitabine was the most frequently used drug for chemotherapy.ConclusionsThis study established the general patterns of RT practice for BTC in Japan. Further surveys and comparisons with results from other countries are needed for development and optimization of RT for patients with BTC in Japan.

Is the outcome of a salvage surgery for T4 thoracic esophageal squamous cell carcinoma really poor

BackgroundAmong patients with T4 thoracic esophageal squamous cell carcinoma (TESCC), it is unclear whether the outcomes of late responders who undergo high-dose chemoradiotherapy (CRT) followed by salvage esophagectomy differs from those of early responders who undergo low-dose CRT followed by esophagectomy.MethodsA total of 153 patients with T4 TESCC were treated with CRT. The first evaluation was performed after 40xa0Gy of CRT for downstaging. Of these, 28 patients could be downstaged, and underwent subsequent surgery (early responders). For the remaining patients, additional CRT was administered, and patients were re-evaluated after treatment and underwent salvage surgery. In total, 40 patients (earlyxa0+xa0late responders) were analyzed.ResultsThe primary tumors exhibited a grade 3 response in six (21.4xa0%) of the early responders and two (16.7xa0%) of the late responders (pxa0=xa01.000). The rate of residual tumor in the primary tumor was 80xa0% (32/40 patients). The proportions of resected lymph nodes and positive metastatic nodes were similar between early and late responders (pxa0=xa00.406 and pxa0=xa00.859, respectively). The 5-year overall survival rates among the early and late responders were 25.9 and 36.5xa0%, respectively, and the median survival times were 24.8 and 24.3xa0months (pxa0=xa00.925), respectively. The 5-year cause-specific survival rates in the early and late responder groups were 61.5 and 72.9xa0% (pxa0=xa00.425), respectively.ConclusionThe outcomes of both early and late responders to CRT were similar, and salvage surgery for T4 TESCC outweighs the risks in patients with T4 TESCC.

New approach to relieving pain and distress during high-dose-rate intracavitary irradiation for cervical cancer

BACKGROUND AND PURPOSEnTo relieve the pain and distress experienced by women who undergo high-dose-rate intracavitary radiotherapy (HDR-ICRT) for cervical cancer and to improve the current status of gynecologic brachytherapy in Japan, a new intravenous anesthetic protocol involving the administration of a combination of propofol and ketamine was developed. The primary aim of this study is to investigate the efficacy and safety of this new anesthetic protocol during HDR-ICRT for cervical cancer.nnnMETHODS AND MATERIALSnAll the patients who were diagnosed with cervical cancer between December 2008 and February 2011, treated with three-channel brachytherapy and subjected to the new sedation protocol, were evaluated. A visual analog scale (VAS) was used to assess the pain during brachytherapy, and we collected VAS score at the next HDR-ICRT. Toxicities were graded using the Common Toxicity Criteria, versionxa03.nnnRESULTSnA total of 178 sessions of HDR-ICRT were delivered to 57 patients. The patients median VAS pain score was 0 (range, 0-10). The most frequent side effect was Grade 1-2 nausea, which occurred in 33 sessions (34%). However, 13 of 14 patients received concurrent cisplatin chemotherapy. None of the patients experienced Grade 3 or 4 adverse events.nnnCONCLUSIONSnWe have demonstrated that our new intravenous anesthetic protocol produces appropriate effects and can be performed by radiation oncologists who were required to finish training in basic life support and the cooperative system of emergency according to in-house guideline.

Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles

Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy).