Necrotizing fasciitis wound after debridement could be successfully treated with negative-pressure wound therapy with instillation and dwelling: A case report.

Background: Necrotizing fasciitis (NF) is associated with a high mortality rate. Adequate incision and drainage and repeated debridement are necessary for NF management. After drainage, daily local irrigation should be performed. Case presentation: A 72-year-old male patient complained of left lower quadrant pain. Computed tomography revealed a 7 cm mass in the descending colon, with retroperitoneal penetration. Hence, he underwent emergency surgery. The left abdomen was widely incised, and a transverse colostomy was performed for local wound control. Daily debridement of necrotic tissue and wound irrigation were continued. On postoperative day 48, the wound was extensive and complex and obtained a positive bacterial culture. Subsequently, we began a negative-pressure wound therapy with instillation and dwelling (NPWTi-d), which was very effective for extensive and complicated wounds with infection. Thereafter, a split-thickness skin was grafted, and the skin graft survived well. Ultimately, the wound successfully closed. Conclusions: NPWT is contraindicated for infected wounds, and an infection control period is required. However, NPWTi-d enables early initiation of wound care despite the presence of infection. Therefore, NPWTi-d is effective for extensive and complicated wounds with infection after NF debridement.

Carbon-ion radiotherapy for oligometastatic liver disease: A national multicentric study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS).

Reports on the therapeutic efficacy and safety of carbon-ion radiotherapy (C-ion RT) for oligometastatic liver disease are limited, with insufficient evidence. This study aimed to evaluate the clinical outcomes of C-ion RT for oligometastatic liver disease at all Japanese facilities using the nationwide cohort data. We reviewed the medical records to obtain the nationwide cohort registry data on C-ion RT between May 2016 and June 2020. Patients (1) with oligometastatic liver disease as confirmed by histological or diagnostic imaging, (2) with ≤3 synchronous liver metastases at the time of treatment, (3) without active extrahepatic disease, and (4) who received C-ion RT for all metastatic regions with curative intent were included in this study. C-ion RT was performed with 58.0-76.0 Gy (relative biological effectiveness [RBE]) in 1-20 fractions. In total, 102 patients (121 tumors) were enrolled in this study. The median follow-up duration for all patients was 19.0 months. The median tumor size was 27 mm. The 1-year/2-year overall survival, local control, and progression-free survival rates were 85.1%/72.8%, 90.5%/78.0%, and 48.3%/27.1%, respectively. No patient developed grade 3 or higher acute or late toxicity. C-ion RT is a safe and effective treatment for oligometastatic liver disease and may be beneficial as a local treatment option in multidisciplinary treatment.

A Japanese registry study and systematic review of particle therapy for renal cell carcinoma.

The feasibility and efficacy of particle beam therapy (PBT) using protons or carbon ions were compared with those of photon-based stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC) via a systematic review and nationwide registry for PBT (Japanese Society for Radiation Oncology [JASTRO] particle therapy committee). Between July 2016 and May 2019, 20 patients with non-metastatic RCC who were treated at six Japanese institutes (using protons at three, using carbon ions at the other three) were registered in the nationwide database and followed up prospectively. The 20 patients comprised 15 men and had a median age of 67 (range: 57-88) years. The total radiation dose was 66-79.6 Gy (relative biological effectiveness [RBE]). Over a median follow up of 31 months, the 3-year rates of overall survival (OS) and local control (LC) were 100% and 94.4%, respectively. No grade ≥ 3 toxicities were observed. Based on a random effects model, a meta-analysis including the present results revealed 3-year OS rates after SBRT and PBT of 75.3% (95% CI: 57.3-86.6) and 94.3% (95% CI: 86.8-97.6), respectively (P = 0.005), but the difference in LC rates between the two methods was not observed (P = 0.63). PBT is expected to have similar if not better treatment results compared with SBRT for primary renal cancer. In particular, PBT was shown to be effective even for large RCC and could provide a therapeutic option when SBRT is not indicated.

Carbon-ion radiotherapy for cholangiocarcinoma: a multi-institutional study by and the Japan carbon-ion radiation oncology study group (J-CROS).

To evaluate the safety and efficacy of carbon-ion radiotherapy (CIRT) for cholangiocarcinoma via a multicenter retrospective study. Clinical data were collected from patients with cholangiocarcinoma who had received CIRT at one of four treating institutions in Japan. Of 56 eligible patients, none received surgery for cholangiocarcinoma before or after CIRT. The primary endpoint was overall survival (OS). Based on the tumor site, the 56 cases were categorized as intrahepatic cholangiocarcinoma (IHC) (n=27) or perihilar cholangiocarcinoma (PHC) (n=29). In all patients, the median tumor size was 37 (range, 15‒110) mm, and the most commonly prescribed dose was 76 Gy (relative biological effectiveness) in 20 fractions. The median survival was 14.8 (range, 2.1-129.2) months, and the 1- and 2-year OS rates were 69.7% and 40.9%, respectively. The median survival times of the patients with IHC and those with PHC were 23.8 and 12.6 months, respectively. Both univariate and multivariate analyses revealed that cholangitis pre-CIRT and Child‒Pugh class B were significant prognostic factors for an unfavorable OS. Of four patients who died of liver failure, one with IHC was suspected to have radiation-induced liver disease because of newly developed ascites, and died at 4.3 months post-CIRT. Grade 3 CIRT-related bile duct stenosis was observed in one IHC case. No other CIRT-related severe adverse events, including gastrointestinal events, were observed. These results suggest that CIRT yields relatively favorable treatment outcomes, especially for patients with IHC, and acceptable toxicities were observed in patients with cholangiocarcinoma who did not receive surgery.

Short-course carbon-ion radiotherapy for hepatocellular carcinoma: A multi-institutional retrospective study.

BACKGROUND & AIMS: Carbon-ion radiation therapy has shown encouraging results in hepatocellular carcinoma patients in single-centre studies. We evaluated the effectiveness and safety of short-course carbon-ion radiation therapy for hepatocellular carcinoma in a multicentre study conducted by the Japan Carbon Ion Radiation Oncology Study Group. METHODS: Consecutive hepatocellular carcinoma patients who were treated with carbon-ion radiation therapy in four or fewer fractions at four Japanese institutions between April 2005 and November 2014 were analysed retrospectively. The primary outcome was overall survival; secondary outcomes were local control rate, treatment-related toxicity and radiation-induced liver disease. RESULTS: A total of 174 patients were included in this study. Prescribed carbon-ion radiation therapy doses were (relative biological effectiveness): 48.0 Gy in two fractions (n = 46), and 52.8 Gy (n = 108) and 60.0 Gy (n = 20) in four fractions. The median follow-up period was 20.3 (range, 2.9-103.5) months. The overall survival and local control rates at 1, 2 and 3 years were 95.4%, 82.5% and 73.3%; and 94.6%, 87.7% and 81.0% respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status 1-2, Child-Pugh class B, maximum tumour diameter ≥3 cm, multiple tumours and serum alpha foetoprotein level >50 ng/mL were significant prognostic factors of overall survival. No treatment-related death occurred during the follow-up period. Grades 3 or 4 treatment-related toxicities were observed in 10 patients (5.7%); radiation-induced liver disease was observed in three patients (1.7%). CONCLUSIONS: Short-course carbon-ion radiation therapy is a safe, effective and potentially curative therapy for hepatocellular carcinoma.

A single institutional experience of combined carbon-ion radiotherapy and chemotherapy for unresectable locally advanced pancreatic cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for unresectable locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS: Patients with LAPC treated with definitive C-ion RT between April 2014 and July 2017 were analyzed retrospectively. The prescribed dose was 55.2 Gy (relative biological effectiveness [RBE] weighted absorbed dose) in 12 fractions. Overall survival (OS), local control (LC), progression free survival (PFS), and toxicity were evaluated. RESULTS: Sixty-four patients were enrolled. All patients completed planned course of C-ion RT. The median follow-up time for survivors from the initiation of C-ion RT was 24.4 months (range, 5.1-46.1 months). Median survival time was 25.1 months. Two-year OS, LC, and PFS were 53% (95% confidence interval [CI], 39%-66%), 82% (95% CI, 66%-91%), and 23% (95% CI, 14%-36%), respectively. Four patients experienced acute grade 3 toxicities including 3 gastrointestinal (GI) toxicities. There was no grade 3 or more late toxicity. CONCLUSIONS: The clinical results of C-ion RT for LAPC at our institution were comparable to those of a recent multi-institutional analysis.

A case of the cirrhotic patient performed living donor liver transplantation after carbon-ion radiotherapy for hepatocellular carcinoma.

The patient was a 50-year-old female with an initial diagnosis of a single hepatocellular carcinoma in liver cirrhosis. The tumor was located in the posterior liver segment (S7) and measured 5 cm with a rapid growth rate and portal invasion. The pre-treatment Child-Pugh (C-P) was grade A (six points). The total prescribed dose of carbon-ion radiotherapy (C-ion RT) was 60 Gy (relative biological effectiveness) given in 4 fractions. Thereafter, tumor shrinkage and rapid decrease of the serum alpha-fetoprotein level were observed. At 1-year follow-up a new lesion was diagnosed in the left lobe and the underlying liver failure had worsened to C-P grade B (eight points). Thus, she was recommended to undergo living-donor liver transplantation (LDLT). The postoperative course was uneventful. At pathological examination, no viable tumor cells in the region treated with C-ion RT were detected. At the time of the last follow-up, the patient was in overall good general condition with no signs of tumor recurrence.

[Conversion Surgery Combined with Preoperative Coil Embolization of Hepatic Artery for Locally Advanced Unresectable Pancreatic Head Cancer with Hepatic Artery Invasion-A Case Report].

Here we report a case treated with conversion surgery combined with preoperative coil embolization of the hepatic artery after chemoradiation therapy for locally advanced unresectable pancreatic head cancer with hepatic artery invasion. A 63- year-old man was referred to our hospital for treatment of pancreatic cancer. Abdominal CT scan revealed a 30mm pancreatic head tumor with involvement of the common hepatic artery(CHA)and proper hepatic artery(PHA). The left hepatic artery diverged from the left gastric artery. Although S-1 with concurrent radiation therapy was performed, a follow-up CT scan revealed the progression of soft tissue shadow around the CHA. Subsequently, gemcitabine plus nab-paclitaxel(GnP)was administered 13 times. GnP helped achieve normalization of the tumor markers and long stable disease(SD)based on the Response Evaluation Criteria in Solid Tumors(RECIST). For the conversion surgery, embolization of the middle hepatic artery (MHA)was performed. Twelve days after, the right hepatic artery was embolized. Subtotal stomach-preserving pancreaticoduodenectomy was performed with resection of the CHA and PHA without arterial reconstruction 16 days after the hepatic arterial embolization. The patient was discharged from our hospital 33 days after surgery without complications related to hepatic ischemia. The patient is alive without recurrence 42 months after the initial diagnosis and 26 months after surgery.

A multi-institutional analysis of prospective studies of carbon ion radiotherapy for prostate cancer: A report from the Japan Carbon ion Radiation Oncology Study Group (J-CROS).

BACKGROUND AND PURPOSE: A multi-institutional observational study (J-CROS1501PR) has been carried out to analyze outcomes of carbon-ion radiotherapy (CIRT) for patients with prostate cancer. PATIENTS AND METHODS: Data of the patients enrolled in prospective studies of following 3 CIRT institutions were analyzed: National Institute of Radiological Sciences (NIRS; Chiba, Japan), Gunma University Heavy Ion Medical Center (GHMC; Gunma, Japan), and Ion Beam Therapy Center, SAGA HIMAT Foundation (HIMAT; Saga, Japan). Endpoints of the clinical trial are biochemical recurrence-free survival (bRFS), overall survival (OS), cause-specific survival (CSS), local control rate (LCR), and acute/late adverse effects. RESULTS: A total of 2157 patients' data were collected from NIRS (n=1432), GHMC (n=515), and HIMAT (n=210). The number of patients in low-risk, intermediate-risk, and high-risk groups was 263 (12%), 679 (31%), and 1215 (56%), respectively. The five-year bRFS in low-risk, intermediate-risk, and high-risk patients was 92%, 89%, and 92%, respectively. The five-year CSS in low-risk, intermediate-risk, and high-risk patients was 100%, 100%, and 99%, respectively. The incidence of grade 2 late GU/GI toxicities was 4.6% and 0.4%, respectively, and the incidence of ⩾G3 toxicities were 0%. CONCLUSIONS: Favorable overall outcomes of CIRT for prostate cancer were suggested by the analysis of the first multi-institutional data.

Dosimetric analysis of upper gastrointestinal ulcer after carbon-ion radiotherapy for pancreatic cancer.

PURPOSE: The aim of this study was to clarify the incidence, clinical risk factors, and dose-volume relationship of upper gastrointestinal (GI) ulcer after carbon-ion radiotherapy (C-ion RT) for pancreatic cancer. MATERIALS AND METHODS: Fifty-eight pancreatic cancer patients were treated with C-ion RT from April 2014 to December 2015. The total dose was 55.2Gy (RBE) in 12 fractions. D2cm3 of GI tracts were restricted under 46Gy (RBE); RBE-weighted absorbed dose. The association between dosimetric parameters (V10-50, Dmax, D1cm3, D2cm3) and GI ulcer was examined using Spearman's correlation. The incidence of GI ulcer was compared between the two groups divided by the cutoff value. RESULTS: Twelve patients (21%) experienced gastric ulcer including only one (2%) grade 3 ulcer. There was no grade 4/5 toxicity or duodenal ulcer. V10-30 was significantly associated with gastric ulcer. The 1-year estimated risk of gastric ulcer for the determined cutoff values were 51% vs. 10% (V10, ⩾102cm(3) or less), 42% vs. 9% (V20, ⩾24cm(3) or less), 34% vs. 4% (V30, ⩾6cm(3) or less). CONCLUSIONS: The incidence of GI ulcer after C-ion RT was very low with the dose constraint of D2cm3 <46Gy (RBE). To further minimize the risk of GI ulcer, V10-30 should also be reduced.

[A Case of Undifferentiated Carcinoma of the Sigmoid Colon That Responded to Paclitaxel and Carboplatin Chemotherapy].

We report a case of a 72-year-old woman who was initially diagnosed with ovarian cancer with peritoneal carcinomatosis. Systemic chemotherapy consisting of paclitaxel and carboplatin(TC)was administered. Although a partial response(PR)was achieved after the 4 courses of TC, this regimen was discontinued due to severe adverse events. Ten months after discontinuation of TC, because abdominal CT and colonoscopy showed an intra-tumoral abscess caused by invasion of the tumor to the sigmoid colon, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and a Hartmann's operation were performed to control the disease symptoms. Pathological examination revealed that the tumor was an undifferentiated carcinoma of the sigmoid colon. This case report suggests that the TC regimen may be effective for treating undifferentiated carcinoma of the colon.

Carbon-ion radiotherapy for locally advanced primary or postoperative recurrent epithelial carcinoma of the lacrimal gland.

PURPOSE: To evaluate the applicability of carbon ion beams for the treatment of carcinoma of the lacrimal gland with regard to normal tissue morbidity and local tumor control. METHODS AND MATERIALS: Between April 2002 and January 2011, 21 patients with locally advanced primary epithelial carcinoma of the lacrimal gland were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy (CIRT) at the National Institute of Radiological Sciences. Acute radiation toxicity was the primary endpoint of this dose-escalation study and the late toxicity, local control, and overall survival were additionally evaluated as secondary endpoints. Of the 21 subjects enrolled, all patients were followed for more than 6 months and analyzed. RESULTS: The radiation dose was increased from the initial dose of 48.0Gy equivalents (GyE)/12 fractions at 10% increments up to 52.8GyE. Of the 21 patients, five received a total dose of 48.0GyE, and 16 received a total dose of 52.8GyE. No patient developed grade 3 or higher skin toxicity. As late ocular/visual toxicity, three patients had grade 3 retinopathy and seven patients lost their vision. Among the 10 patients treated until May 2005, five patients had local recurrence, three of whom had marginal recurrence. Therefore, the margin for the CTV (clinical target volume) was set to a range according to the orbital exenteration since June 2005. After the application of the extended margin, no local recurrence has been observed. The three-year overall survival and local control rates were 82.2% and 79.0%, respectively. CONCLUSION: CIRT can be applied for primary epithelial carcinoma of the lacrimal gland, with a borderline acceptable morbidity and sufficient antitumor effect when an extended margin is adopted.

Particle radiotherapy for prostate cancer.

Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy.

[A case of a patient with gastric cancer and peritoneal dissemination who survived for more than 10 years after successful treatment with S-1].

A 50-year-old female patient underwent distal gastrectomy and intraperitoneal CDDP administration for advanced gastric cancer accompanied by severe peritoneal dissemination. She valued her quality of life and chose an oral anticancer drug, S-1, as a postoperative chemotherapy agent. S-1 was administered at a dose of 100mg/body/day for 4 weeks, followed by a 2- week rest. There were no adverse events due to S-1 and no exacerbation of peritoneal dissemination in the 5 years following surgery. The S-1 administration schedule was then changed to alternate-day administration. Eight years after the surgery, the patient discontinued S-1 treatment and has since survived for 11 years with no obvious cancer recurrence.

Management of high-risk prostate cancer: radiation therapy and hormonal therapy.

The prognosis of high-risk prostate cancer is poor with a high mortality rate. The Radiation Therapy Oncology Group (RTOG) has performed dose-escalation studies of external beam radiation therapy (EBRT) and has developed high-precision radiation therapy (RT) methods such as intensity-modulated RT, carbon ion therapy, and proton beam therapy. High-dose rate brachytherapy (HDR-BT) is also studied as an option for high-risk prostate cancer treatment. Past clinical trials have suggested that the local control rate of high-risk prostate cancer improves with total EBRT dose, even for doses > 70 Gy. Several randomized controlled trials, including RTOG 94-06, have shown significantly better prognoses with higher doses (> 75 Gy) than with lower doses (< 70 Gy). A proton beam therapy trial (PROG 95-09) also showed similar results. A phase II clinical trial (National Institute for Radiological Sciences, Japan; trial 9904) showed that carbon ion therapy resulted in very good biochemical recurrence-free survival rates among high-risk prostate cancer patients, demonstrating particle therapy to be a valid treatment option. RTOG 86-10 showed that short-term neo-adjuvant hormonal therapy (HT) was inadequate for high-risk prostate cancer but effective for intermediate-risk prostate cancer, whereas RTOG 92-02 and the European Organisation for Research and Treatment of Cancer (EORTC) 22863 showed significant improvements in the prognosis of high-risk groups receiving long-term (> 2 years) HT combined with definitive RT. Further studies are warranted to elucidate optimal irradiation doses, HT treatment durations, and combination therapy schedules.

Long-term results of carbon ion radiation therapy for locally advanced or unfavorably located choroidal melanoma: usefulness of CT-based 2-port orthogonal therapy for reducing the incidence of neovascular glaucoma.

PURPOSE: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). METHODS AND MATERIALS: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. RESULTS: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. CONCLUSIONS: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.