Definitive chemoradiotherapy for a patient with anal cancer after renal transplantation.

Patients after renal transplantation are susceptible to secondary malignancies, including anal squamous cell carcinoma. Chemoradiotherapy is the standard treatment for anal squamous cell carcinoma; however, typical irradiation fields for anal cancer encompass a transplanted kidney located in the right iliac fossa, which causes complete renal dysfunction. Thus, typical irradiation fields are not feasible for this population. Additionally, standard concurrent chemotherapy demonstrates nephrotoxicity. Here, we report a case of modified definitive chemoradiotherapy for a 40-year-old patient with locally advanced perianal squamous cell carcinoma after renal transplantation whose abdominoperineal resection was difficult because of a history of repeated open surgeries and long-term steroids. We modified the cranial side of the elective nodal irradiation fields in this case to spare the transplanted kidney, considering the lymph chains of the perianal tumor. We then used continuous 5-fluorouracil to avoid nephrotoxicity of mitomycin C, considering his life expectancy. Modified definitive chemoradiotherapy achieved complete remission with expected toxicities. Now, approximately five years after the procedure, the patient remains disease-free, preserving anal and renal function. Definitive chemoradiotherapy using modified irradiation fields and chemotherapy may be an option for patients with anal squamous cell carcinoma after renal transplantation.

Recurrence patterns and progression-free survival after chemoradiotherapy with or without consolidation durvalumab for stage III non-small cell lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

A case of a pregnant woman with locally advanced cervical esophageal cancer treated with definitive chemoradiotherapy.

The information of definitive radiotherapy for a pregnant woman with malignancy was limited; however, it was reported to be potentially feasible with minimal risks. We performed definitive chemoradiotherapy for a pregnant woman with locally advanced cervical esophageal cancer. Feasibility of radiotherapy and safety of fetus were confirmed by the phantom study estimating fetal dose, and monitoring it in each radiotherapy session. The planned chemoradiotherapy completely eradicated esophageal cancer while preserving her laryngopharyngeal function. A female infant was delivered by cesarian section after planned chemoradiotherapy, and she grew without any apparent disorders 2 years after chemoradiotherapy. Chemoradiotherapy might be one of the treatment options for a pregnant woman with cervical esophageal cancer especially wishing the preservation of laryngopharyngeal function.

Association of volumetric-modulated arc therapy with radiation pneumonitis in thoracic esophageal cancer.

The lung volume receiving low-dose irradiation has been reported to increase in volumetric-modulated arc radiotherapy (VMAT) compared with three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal cancer, which raises concerns regarding radiation pneumonitis (RP) risk. This single institutional retrospective cohort study aimed to explore whether VMAT for thoracic esophageal cancer was associated with RP. Our study included 161 patients with thoracic esophageal cancer, of whom 142 were definitively treated with 3DCRT and 39 were treated with VMAT between 2008 and 2018. Radiotherapy details, dose-volume metrics, reported RP risk factors and RP incidence were collected. The RP risk factors were assessed via multivariate analysis. Dose-volume analysis showed that VMAT delivered more conformal dose distributions to the target volume (P < 0.001) and reduced V30 Gy of heart (57% vs 41%, P < 0.001) but increased V5 Gy (54% vs 41%, P < 0.001) and V20 Gy (20% vs 17%, P = 0.01) of lungs compared with 3DCRT. However, the 1-year incidence rates of RP did not differ between the two techniques (11.3% in 3DCRT vs 7.7% in VMAT, P = 0.53). The multivariate analysis suggested that the presence of interstitial lung disease (ILD) (P = 0.01) and V20 Gy of lungs ≥20% (P = 0.008) were associated with RP. Conclusively, VMAT increased the lung volume receiving low to middle doses irradiation, although this might not be associated with RP. Further studies are needed to investigate the effect of using VMAT for delivering conformal dose distributions on RP.

Rapidly Growing Locally Advanced Non-Small Cell Lung Cancer Treated with Definitive Chemoradiotherapy Using Adaptive Volumetric Modulated Arc Therapy Followed by Durvalumab Maintenance: A Case Report.

BACKGROUND It is difficult to reduce lung toxicity in chemoradiotherapy for locally advanced lung cancer. Volume-modulated arc therapy (VMAT) is a useful lung dose-lowering radiation technique, but it is time-consuming because of its complexity. We present a case of a rapidly growing bulky lung cancer treated with VMAT and intensive adaptation to volume change. CASE REPORT A 43-year-old man with chest pain was diagnosed with non-small cell lung cancer, cT4N3M0 stage IIIC (UICC 8th edition). Concurrent chemoradiotherapy with a VMAT of 60 Gy in 30 fractions and carboplatin/paclitaxel was performed. Despite initiating chemoradiation, monitoring with cone-beam computed tomography (CT) revealed tumor progression. The peak tumor volume was 1.5 times larger than that on CT simulation. The VMAT plan was recreated to cover the increased tumor size. After the irradiation field was enlarged, the tumor, on the contrary, shrank rapidly. Therefore, VMAT planning was performed again to further shrink the irradiation field. CT at the end of the treatment showed a good volume reduction response. Durvalumab therapy was continued for 1 year. After that, the patient was alive and showed no sign of progression. Only asymptomatic radiation pneumonitis was observed as a sub-acute adverse event. CONCLUSIONS We present a case in which proper adaptive VMAT and durvalumab for dramatically progressive non-small cell lung cancer were effective, resulting in 1-year progression-free survival. Even when rapid progression of bulky lung cancer is suggested, the combination of VMAT and adaptive radiotherapy with improved target coverage and reduced lung dose can be a treatment option.

Preoperative chemoradiotherapy for locally advanced low rectal cancer using intensity-modulated radiotherapy to spare the intestines: a single-institutional pilot trial.

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3-4, N0-2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V15 Gy) < 120 cc and V45 Gy ≤ 0 cc, respectively, while keeping target coverage. S-1 and irinotecan were concurrently administered. Acute gastrointestinal toxicity, rates of clinical downstaging, sphincter preservation, local regional control (LRC) and overall survival (OS) were evaluated. Twelve enrolled patients completed the chemoradiotherapy protocol. The volumes of intestines receiving medium to high doses were reduced by the current IMRT protocol compared to 3DCRT; however, the predefined constraint of V15 Gy was met only in three patients. The rate of ≥ grade 2 gastrointestinal toxicity excluding anorectal symptoms was 17%. The rates of clinical downstaging, sphincter preservation, three-year LRC and OS were 75%, 92%, 92% and 92%, respectively. In conclusion, preoperative chemoradiotherapy using IMRT for this population might alleviate acute gastrointestinal toxicity, achieving high LRC and sphincter preservation; although further advancement is required to reduce the irradiated volume of intestines, especially those receiving low doses.

Chemoradiotherapy for fistula-related perianal squamous cell carcinoma with Crohn's disease.

The reports of chemoradiotherapy for anal squamous cell carcinoma with Crohn's disease are few. Severe toxicity related to radiotherapy is concerned in patients with inflammatory bowel disease. We report a case of chemoradiotherapy for locally advanced fistula-related perianal squamous cell carcinoma in a patient with long-standing Crohn's disease which was controlled by a maintenance therapy. The patient completed standard chemoradiotherapy using intensity-modulated radiotherapy without severe toxicity, and achieved complete remission. Standard chemoradiotherapy using intensity-modulated radiotherapy may be feasible and effective treatment for this population when Crohn's disease is controlled.

Reducing variability among treatment machines using knowledge-based planning for head and neck, pancreatic, and rectal cancer.

PURPOSE: This study aimed to assess dosimetric indices of RapidPlan model-based plans for different energies (6, 8, 10, and 15 MV; 6- and 10-MV flattening filter-free), multileaf collimator (MLC) types (Millennium 120, High Definition 120, dual-layer MLC), and disease sites (head and neck, pancreatic, and rectal cancer) and compare these parameters with those of clinical plans. METHODS: RapidPlan models in the Eclipse version 15.6 were used with the data of 28, 42, and 20 patients with head and neck, pancreatic, and rectal cancer, respectively. RapidPlan models of head and neck, pancreatic, and rectal cancer were created for TrueBeam STx (High Definition 120) with 6 MV, TrueBeam STx with 10-MV flattening filter-free, and Clinac iX (Millennium 120) with 15 MV, respectively. The models were used to create volumetric-modulated arc therapy plans for a 10-patient test dataset using all energy and MLC types at all disease sites. The Holm test was used to compare multiple dosimetric indices in different treatment machines and energy types. RESULTS: The dosimetric indices for planning target volume and organs at risk in RapidPlan model-based plans were comparable to those in the clinical plan. Furthermore, no dose difference was observed among the RapidPlan models. The variability among RapidPlan models was consistent regardless of the treatment machines, MLC types, and energy. CONCLUSIONS: Dosimetric indices of RapidPlan model-based plans appear to be comparable to the ones based on clinical plans regardless of energies, MLC types, and disease sites. The results suggest that the RapidPlan model can generate treatment plans independent of the type of treatment machine.

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab.

INTRODUCTION: Data on the risk factors for symptomatic radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors. MATERIALS AND METHODS: This multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP. RESULTS: In the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007). CONCLUSION: The incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.

Association of Chemoradiotherapy With Thoracic Vertebral Fractures in Patients With Esophageal Cancer.

Importance: The association of chemoradiotherapy (CRT) with a thoracic vertebral fracture in patients with esophageal cancer is unknown. Objective: To determine whether CRT is associated with thoracic vertebral fractures in patients with esophageal cancer. Design, Setting, and Participants: This retrospective cohort study included patients with clinical stages I to III thoracic esophageal cancer who visited the Kyoto University Hospital, Kyoto, Japan, from January 1, 2007, to December 31, 2013. Data were analyzed from April 6, 2018, to June 4, 2020. Exposures: Chemoradiotherapy (CRT group) or surgery or endoscopic treatment (non-CRT group). Main Outcomes and Measures: The main outcome of this study was the cumulative incidence rate of thoracic vertebral fractures in 36 months. The incidence rate was calculated taking censoring into account. Possible risk factors, including CRT, were explored in the multivariable analysis. The association of irradiated doses with fractured vertebrae was also evaluated. Results: A total of 315 patients (119 for the CRT group and 196 for the non-CRT group) were included. The median age of patients was 65 (range, 32-85) years. Fifty-six patients (17.8%) were female and 259 (82.2%) were male. The median observation time was 40.4 (range, 0.7-124.1) months. Thoracic vertebral fractures were observed in 20 patients (16.8%) in the CRT group and 8 patients (4.1%) in the non-CRT group. The 36-month incidence rate of thoracic vertebral fractures was 12.3% (95% CI, 7.0%-19.1%) in the CRT group and 3.5% (95% CI, 1.3%-7.5%) in the non-CRT group (hazard ratio [HR], 3.41 [95% CI, 1.50-7.73]; P = .003). The multivariable analysis showed that the HR of the thoracic vertebral fracture in the CRT group to non-CRT group was 3.91 (95% CI, 1.66-9.23; P = .002) with adjusting for sex, 3.14 (95% CI, 1.37-7.19; P = .007) with adjusting for age, and 3.10 (95% CI, 1.33-7.24; P = .009) with adjusting for the history of vertebral or hip fractures. The HR of the thoracic vertebral fracture for a 5-Gy increase in the mean radiation dose to the single vertebra was 1.19 (95% CI, 1.04-1.36; P = .009). Conclusions and Relevance: This study found that chemoradiotherapy was associated with thoracic vertebral fractures in patients with esophageal cancers. A reduced radiation dose to thoracic vertebrae may decrease the incidence of fractures.

Therapy-Related Acute Myeloid Leukemia 2 Months after Chemoradiotherapy for Esophageal Cancer: A Case Report.

Therapy-related acute myeloid leukemia (AML) is a rare but potentially fatal adverse event caused by chemotherapy or radiotherapy. Herein we report a patient diagnosed with therapy-related AML 2 months after chemoradiotherapy for esophageal cancer. A 61-year-old man with dysphagia was diagnosed with locally advanced esophageal cancer with para-aortic lymph node metastasis. Laboratory blood test did not reveal any abnormality except mild macrocytic anemia. To alleviate dysphagia due to malignant esophageal stenosis, the patient underwent concurrent chemoradiotherapy of 60 Gy in 30 fractions with cisplatin and 5-fluorouracil at a local area in thoracic esophagus. Dysphagia alleviated during chemoradiotherapy; however, pancytopenia did not recover after the completion of chemoradiotherapy, and general fatigue with fever developed 13 weeks after the last day of chemoradiotherapy. To rule out hematological malignancy, bone marrow biopsy was performed. The bone marrow smear and flow cytometry analysis indicated the development of AML. Chromosomal test revealed a complex karyotype, suggesting that AML was associated with myelodysplastic syndrome. The patient died 1 month after the diagnosis of therapy-related AML. Thus, the findings indicate that therapy-related AML may develop during the acute phase of chemoradiotherapy and bone marrow biopsy is necessary when prolonged pancytopenia exists after chemoradiotherapy.

Adaptive radiotherapy in locally advanced esophageal cancer with atelectasis: a case report.

BACKGROUND: To the best of our knowledge, no study has reported mediastinal shift accompanied with obstructive atelectasis due to bulky primary esophageal tumor components treated with adaptive radiotherapy and concurrent chemotherapy. CASE PRESENTATION: Here we report the case of a 65-year-old male patient diagnosed with locally advanced thoracic esophageal squamous cell cancer, clinical T4bN1M0, stage IVA. Bronchoscopy and computed tomography (CT) revealed an almost complete obstruction of the lumen of the left bronchus due to compression by bulky primary esophageal tumor components. On admission, the patient presented with dyspnea and decreased arterial oxygen saturation. Chest radiography and CT on admission revealed mediastinal shift with left atelectasis, as opposed to findings from the chest radiography performed 26 days before admission. Because of the patient's overall good condition, we recommended definitive chemoradiotherapy instead of palliative bronchial stent placement. After obtaining the patient's consent, chemoradiotherapy was initiated on the following day and it comprised three-dimensional conformal radiotherapy with 60 Gy in 30 fractions with concurrent administration of cisplatin and 5-fluorouracil. During chemoradiotherapy, tumor location was monitored with cone-beam CT and chest radiography. Chemoradiotherapy on day 8 revealed no evidence of the mediastinal shift. CT simulation was reperformed to adjust the radiotherapy fields to account for geometrical changes induced by the absence of the mediastinal shift. Subsequently, the mediastinal shift and bronchial obstruction did not recur during the course of chemoradiotherapy. The patient completed the planned radiotherapy with concurrent and adjuvant chemotherapy, and no non-hematological grade ≥ 3 adverse events were observed. Complete response was confirmed 7 months after initiating chemoradiotherapy. Currently, no disease recurrence, dysphagia, or respiratory symptoms have been reported at 13 months after initiating chemoradiotherapy. CONCLUSIONS: In this study, a bulky primary esophageal tumor caused mediastinal shift due to ipsilateral bronchial obstruction. The close follow-up for monitoring resolution of the mediastinal shift during the course of chemoradiotherapy enabled adequate dose delivery to targets, thus reflecting the geometrical changes induced by the absence of the mediastinal shift. Adaptive radiotherapy technique was crucial for favorable patient outcomes in this challenging clinical situation.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma without hypopharyngeal invasion: dose distribution and clinical outcome.

Hypopharyngeal invasion would be a key finding in determining the extent of the irradiation fields in patients with cervical esophageal squamous cell carcinoma (CESCC). This study aimed to investigate the clinical outcomes of chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) omitting upper cervical lymph nodal irradiation in CESCC without hypopharyngeal invasion, and the dosimetric superiority of SIB-IMRT to 3D conformal radiotherapy (3DCRT). We retrospectively identified 21 CESCC patients without hypopharyngeal invasion [clinical Stage I/II/III/IV (M1LYM); 3/6/5/7] (UICC-TNM 7th edition) who underwent chemoradiotherapy using SIB-IMRT between 2009 and 2015. SIB-IMRT delivered 60 Gy to each primary tumor and the metastatic lymph nodes, and 48 Gy to elective lymph nodal regions, including Levels III and IV of the neck, supraclavicular, and upper mediastinal lymphatic regions, in 30 fractions. The overall survival rate, locoregional control rate, and initial recurrence site were evaluated. 3DCRT plans were created to perform dosimetric comparisons with SIB-IMRT. At a median follow-up of 64.5 months, the 5-year locoregional control and overall survival rates were 66.7% and 53.4%, respectively. Disease progressed in eight patients: all were locoregional progressions and no patients developed distant progression including upper cervical lymph nodal regions as initial recurrence sites. The planning study showed SIB-IMRT improved target coverage without compromising the dose to the organs at risk, compared with 3DCRT. In conclusion, omitting the elective nodal irradiation of the upper cervical lymph nodes was probably reasonable for CESCC patients without hypopharyngeal invasion. Locoregional progression remained the major progression site in this population.

Nutritional and clinical outcomes of chemoradiotherapy for clinical T1N0M0 esophageal carcinoma.

Purpose: Whether nutritional assessment and management improves clinical outcomes in patients with clinical T1N0M0 esophageal squamous cell carcinoma (ESCC) who undergo chemoradiotherapy remains to be demonstrated. This study aimed to determine the nutritional status of such patients pre- and post-chemoradiotherapy and its clinical outcomes. Patients and methods: This single institutional retrospective study included patients who underwent chemoradiotherapy for clinical T1N0M0 ESCC using serum albumin concentrations and body weights evaluated pre- and post-chemoradiotherapy from January 2005 to December 2016. The nutritional risk index (NRI) score was used to quantify the nutritional status: NRI score ≥100: no risk, 97.5-100: mild risk, 83.5-97.5: moderate risk, and <83.5: major risk. NRI categories pre-and post-chemoradiotherapy were compared using Wilcoxon signed rank test. Local-regional control (LRC), overall survival (OS), and cause-specific survival (CSS) rates were calculated using Kaplan-Meier method. The effect of pre-chemoradiotherapy NRI score and decreased NRI category during chemoradiotherapy on OS was evaluated using log-rank test. Results: Among the 492 patients with ESCC who underwent chemoradiotherapy, 44 were included in this study. Among these, 21 patients exhibited a pre-chemoradiotherapy NRI score of <100. During chemoradiotherapy, the NRI score decreased from 100.5 to 94.5, and the median NRI category significantly decreased by 2 (p<0.0001). With a median follow-up of 72 months, the 5-year LRC, OS, and CSS rates were 79.8%, 88.9%, and 96.8%, respectively. The pre-chemoradiotherapy NRI score of <100 and decreased NRI category during chemoradiotherapy did not significantly affect OS. Conclusion: Patients with clinical T1N0M0 ESCC without dysphagia were at risk of undernutrition pre- and post-chemoradiotherapy. The current study's results justify further clinical nutritional research for this population, and that clinicians consider nutritional support for this population.

Long-term outcome of definitive radiotherapy for cervical esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to identify the long-term clinical outcome of definitive radiotherapy using three-dimensional conformal radiotherapy (3DCRT) for cervical esophageal squamous cell carcinoma (CESCC). METHODS: We retrospectively reviewed the medical records of 30 patients with CESCC [clinical stage I/II/III/IV(M1LYM); 3/2/12/13] (TNM 7th edition) who underwent definitive radiotherapy using 3DCRT between 2000 and 2014 in our institution. The median prescribed dose for the gross tumor and metastatic lymph nodes was 60 Gy. Twenty-six patients underwent elective nodal irradiation for the neck node levels III, IV, and VI and for upper mediastinal lymph nodes with a median dose of 40 Gy. Twenty-six patients underwent concurrent chemotherapy. Initial disease progression sites, locoregional control (LRC) rate, overall survival (OS) rate, and toxicities were retrospectively evaluated. A univariate analysis was performed to identify prognostic factors. RESULTS: With a median follow-up of 110 months, the 5- and 10-year LRC rates were 43.7% and 37.4%, respectively. The 5- and 10-year OS rates were 48.3% and 40.2%, respectively. Locoregional, distant and both area accounted for 83%, 6% and 11% of the initial progression sites. Unresectable status and M1LYM were significantly associated with poor LRC (p < 0.05) and OS (p < 0.05). Grade 3 acute non-hematological toxicity occurred in 13.3% of patients. During the follow-up, patients without any disease progression did not need a permanent gastrostomy tube or tracheostomy. Late toxicity events, including hypothyroidism and cardiovascular disease, were observed; 5- and 10-year cumulative incidence rates of grade 2 hypothyroidism and ≥grade 3 cardiovascular disease were 31.6% and 62.5%, and 17.5% and 21.3%, respectively. CONCLUSIONS: Definitive radiotherapy yields a cure for patients with CESCC while preserving their laryngopharyngeal function. The poor LRC rate in the advanced stage needs to be overcome for a better prognosis. As the incidence of radiation-induced hypothyroidism and cardiovascular disease was not low, long-term survivors should be followed up for these symptoms.

Dosimetric advantages and clinical outcomes of simultaneous integrated boost intensity-modulated radiotherapy for anal squamous cell carcinoma.

PURPOSE: The purpose of this study was to explore the dosimetric difference between simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and three-dimensional conformal radiotherapy (3DCRT), and the clinical outcomes of anal squamous cell carcinoma (ASCC) chemoradiotherapy featuring SIB-IMRT. MATERIALS AND METHODS: This study included ten patients with ASCC who underwent chemoradiotherapy using SIB-IMRT with 5-fluorouracil and mitomycin C. SIB-IMRT delivered 54 Gy to each primary tumor plus metastatic lymph nodes and 45 Gy to regional lymph nodes, in 30 fractions. Four patients received additional boosts to the primary tumors and metastatic lymph nodes; the median total dose was 54 Gy (range, 54 to 60 Gy). We additionally created 3DCRT plans following the Radiation Therapy Oncology Group 9811 protocol to allow dosimetric comparisons with SIB-IMRT. Locoregional control, overall survival, and toxicity were calculated for the clinical outcome evaluation. RESULTS: Compared to 3DCRT, SIB-IMRT significantly reduced doses to the external genitalia, bladder, and intestine, delivering the doses to target and elective nodal region. At a median follow-up time of 46 months, 3-year locoregional control and overall survival rates were 88.9% and 100%, respectively. Acute toxicities were treated conservatively. All patients completed radiotherapy with brief interruptions (range, 0 to 2 days). No patient experienced ≥grade 3 late toxicity during the follow-up period. CONCLUSION: The dosimetric advantages of SIB-IMRT appeared to reduce the toxicity of chemoradiotherapy for ASCC achieving high locoregional control in the extended period.

[A recurrent gastric cancer with peritoneal metastasis 15 years after distal gastrectomy successfully treated with S-1 and weekly intravenous and intraperitoneal injections of Paclitaxel].

Fifteen years after receiving a distal gastrectomy for advanced gastric cancer, a 70-year-old woman was admitted to our hospital because of abdominal fullness due to ascites. Although cytological examination showed adenocarcinoma cells in the fluid, no examination revealed the primary lesion. Peritoneal metastasis was detected via immunohistochemistry using the cell block technique. After chemotherapy failure (S-1 plus CDDP, weekly PTX, and S-1 plus DOC), the patient received S-1 and weekly intravenous and intraperitoneal injections of PTX. The ascites decreased, and she has been doing well. Our experience with this case suggests that S-1 and weekly intravenous and intraperitoneal injections of PTX is a promising means of treating gastric cancer with peritoneal metastasis.

[A case of superior mesenteric artery occlusion with ischemic enteritis after transcatheter therapy].

An 84-year-old female was admitted with sudden-onset upper abdominal pain. Contrast-enhanced computed tomography (CECT) revealed complete occlusion of the superior mesenteric artery (SMA). After transcatheter infusion of urokinase, embolic occlusion resolved. However, the pain recurred when she started eating. CECT revealed a lesion with thickening of the intestinal wall; therefore, laparoscopy-assisted surgery was undertaken. Histological examination yielded a definitive diagnosis of ischemic enteritis caused by SMA occlusion. Rapid diagnosis and treatment are important in SMA occlusion, and careful observation of the clinical course is recommended after transcatheter therapy.

[Pancreatic pseudocyst with fistula to the common bile duct and the duodenum].

A 35-year-old man was hospitalized for severe acute pancreatitis. On the 24th hospital day, CT scan showed a pancreatic pseudocyst in the head of the pancreas. Conservative medical treatment for 1 month was not effective, and CT scan revealed a fistulous communication of the pseudocyst to the common bile duct and duodenum. After the formation of a fistulous communication, we detected common bile duct stones composed of fatty acid calcium and we removed them endoscopically. The pseudocyst gradually decreased in size and disappeared 4 months later. Follow-up CT scan showed no sign of recurrence.

Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximab.

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative patients following treatment with rituximab has been reported increasingly. The aim of this study was to investigate the molecular mechanisms underlying HBV reactivation in an HBsAg-negative patient. HBV was reactivated in a 75-year-old man following chemotherapy with rituximab, without elevation of HBsAg. The patient's full-length HBV genome was cloned and the entire sequence was determined. Transfection studies were performed in vitro using recombinant wild-type HBV (wild-type), the patient's HBV (patient), and two chimeric HBV constructs, in which the preS/S region of the patient and wild-type virus had been exchanged with one another. Secreted HBsAg and intra- and extra-cellular HBV DNA were measured. The number of amino acid substitutions in HBV from this patient was much higher than in previous reports of HBV mutants, such as occult HBV and vaccine escape HBV mutants. Levels of HBsAg and HBV DNA production in vitro were significantly lower in the patient compared to wild-type transfections. From analyses of the chimeric constructs, the altered preS/S region was responsible mainly for this impairment. These results show that highly mutated HBV can reactivate after chemotherapy with rituximab, despite an unusually large number of mutations, resulting in impaired viral replication in vitro. Severe immune suppression, probably caused by rituximab, may permit reactivation of highly mutated HBV. These findings have important clinical implications for the prevention and management of HBV reactivation and may explain partially the mechanism of recent, unusual cases of HBV reactivation.