Keiko Murofushi

Proton beam therapy for metastatic liver tumors

PURPOSE The purpose of this study was to investigate the safety and efficacy of proton beam therapy (PBT) for the treatment of metastatic liver tumors. MATERIAL AND METHODS A total of 140 patients with liver metastasis who received PBT were retrospectively investigated. The main primary tumor sites were the colorectum (60) and the pancreas (19). RESULTS One hundred thirty-three patients (95%) completed treatment. Two patients experienced late adverse effects (rib fracture and cholangitis). The 5-year overall survival (OS) rate was 24%. In the 85 patients with lesions confined to the liver, the 5-year OS rate of was 28%, and in the 55 patients with lesions both inside and outside the liver, it was 16% (P=0.007). Among the patients with lesions confined to the liver, the 5-year OS rate of the 62 patients who received curative treatment was 30%, and that of the 23 patients who received palliative treatment, 23% (P=0.016). Multivariate analysis showed that the treatment strategy (curative and palliative) alone was associated with the OS rate (P=0.02). CONCLUSION PBT is a potentially safe and effective treatment for metastatic liver tumors.

A multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (SHOGUN trial)

PURPOSE This study was designed to evaluate the safety and efficacy of adding oxaliplatin to preoperative chemoradiotherapy (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). PATIENTS AND METHODS This was a multicenter phase II study in patients with histologically proven clinical stage T3 or T4 (any N, M0) LARC. Patients preoperatively received oral S-1 (80 mg/m(2)/day on days 1-5, 8-12, 22-27, and 29-33) and infusional oxaliplatin (60 mg/m(2) days on 1, 8, 22, and 29) plus radiotherapy (50.4 Gy), with a chemotherapy gap in the third week of radiotherapy. Pathological complete response (pCR) was the primary endpoint. Secondary endpoints included toxicity, compliance, R0 resection rate, and downstaging rate. RESULTS A total of 45 patients were enrolled at six centers in Japan. All 45 patients received CRT, and 44 underwent operation. A pCR was achieved in 12 (27.3%) of the 44 patients who underwent surgery. Near-total tumor regression was confirmed in 47.7%. There were no grade 4 adverse events, and 11.1% of the patients had grade 3 adverse events. R0 resection was achieved in 95.5% of the patients. CONCLUSION Preoperative CRT with S-1 plus oxaliplatin had a high pCR rate and a favorable toxicity profile.

Serum miR-143 levels predict the pathological response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer

Recently, several circulating miRNAs have been reported as promising, minimally invasive biomarkers for the diagnosis or prediction of the prognosis in various types of cancer. However, the utility of circulating miRNAs as predictive markers of the cancer response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer is still unclear. To identify circulating serum miRNAs useful for predicting a pathological good response to nCRT, total 18 serum miRNAs of interest were analyzed by real-time polymerase chain reaction in 94 rectal cancer patients treated with nCRT and surgery. Pathological complete response (pCR; Dworak TRG4) and near-pCR (TRG3) were obtained in 12 (13%) and 9 (9%) patients respectively, and we regarded them as nCRT-responders. Of the 18 serum miRNAs, only the serum level of miR-143 was identified significantly associated with a pathological response to nCRT in 94 patients; the serum miR-143 level was significantly lower in nCRT-responders than in non-responders. A multivariate analysis incorporating other clinicopathological factors showed that only the serum miR-143 level was an independent predictor of a good pathological response. The circulating serum miR-143 level may be a novel, non-invasive predictive marker of a response to nCRT in locally advanced rectal cancer patients.Recently, several circulating miRNAs have been reported as promising, minimally invasive biomarkers for the diagnosis or prediction of the prognosis in various types of cancer. However, the utility of circulating miRNAs as predictive markers of the cancer response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer is still unclear. To identify circulating serum miRNAs useful for predicting a pathological good response to nCRT, total 18 serum miRNAs of interest were analyzed by real-time polymerase chain reaction in 94 rectal cancer patients treated with nCRT and surgery. Pathological complete response (pCR; Dworak TRG4) and near-pCR (TRG3) were obtained in 12 (13%) and 9 (9%) patients respectively, and we regarded them as nCRT-responders. Of the 18 serum miRNAs, only the serum level of miR-143 was identified significantly associated with a pathological response to nCRT in 94 patients; the serum miR-143 level was significantly lower in nCRT-responders than in non-responders. A multivariate analysis incorporating other clinicopathological factors showed that only the serum miR-143 level was an independent predictor of a good pathological response. The circulating serum miR-143 level may be a novel, non-invasive predictive marker of a response to nCRT in locally advanced rectal cancer patients.

Proposed definition of the vaginal cuff and paracolpium clinical target volume in postoperative uterine cervical cancer.

PURPOSE The aim of this study was to develop an appropriate definition for vaginal cuff and paracolpium clinical target volume (CTV) for postoperative intensity modulated radiation therapy in patients with uterine cervical cancer. METHODS AND MATERIALS A working subgroup was organized within the Radiation Therapy Study Group of the Japan Clinical Oncology Group to develop a definition for the postoperative vaginal cuff and paracolpium CTV in December 2013. The group consisted of 5 radiation oncologists who specialized in gynecologic oncology and a gynecologic oncologist. A comprehensive literature review that included anatomy, surgery, and imaging fields was performed and was followed by multiple discreet face-to-face discussions and e-mail messages before a final consensus was reached. RESULTS Definitions for the landmark structures in all directions that demarcate the vaginal cuff and paracolpium CTV were decided by consensus agreement of the working group. A table was created that showed boundary structures of the vaginal cuff and paracolpium CTV in each direction. CONCLUSIONS A definition of the postoperative cervical cancer vaginal cuff and paracolpium CTV was developed. It is expected that this definition guideline will serve as a template for future radiation therapy clinical trial protocols, especially protocols involving intensity modulated radiation therapy.

Phase II trial of induction mFOLFOX6 plus bevacizumab followed by neoadjuvant S-1-based chemoradiation for MRI-defined poor-risk rectal cancer.

700 Background: Induction chemotherapy has been explored as a novel treatment option to improve oncological outcomes in poor-risk locally advanced rectal cancer (LARC). Although previous studies have suggested high pCR rate with a favorable toxicity profile in S-1-based neoadjuvant chemoradiation, no study has evaluated induction chemotherapy added with this regimen. The present study is designed to evaluate the safety and efficacy of induction chemotherapy with bevacizumab followed by neoadjuvant S-1 based chemoradiation in MRI-defined poor-risk LARC. Methods: This was a single-center phase II trial at a high-volume cancer center. Eligible patients had low rectal adenocarcinoma with MRI-defined poor-risk features. Patients received 12-week (6 course) mFOLFOX plus bevacizumab (5 mg/kg every 2 weeks) followed by concomitant oral S-1 (80mg/m2/day on days 1-5, 8-12, 22-27, and 29-33) plus radiotherapy (50.4Gy). Surgery was scheduled for 6-10 weeks after chemoradiation. Pathological complete response (pCR) wa...

A validated proton beam therapy patch-field protocol for effective treatment of large hepatocellular carcinoma.

Abstract Development of a curative local treatment for large hepatocellular carcinoma (HCC) is an important issue. Here, we investigated the dose homogeneity, safety and antitumor effectiveness of proton beam therapy (PBT) using a patch-field technique for large HCC. Data from nine patients (aged 52–79 years) with large HCC treated with patch-field PBT were investigated. The cranial–caudal diameters of the clinical target volumes (CTVs) were 15.0–18.6 cm (median 15.9). The CTV was divided cranially and caudally while both isocenters were aligned along the cranial–caudal axis and overlap of the cranial and caudal irradiation fields was set at 0–0.5 mm. Multileaf collimators were used to eliminate hot or cold spots. Total irradiation doses were 60–76.4 Gy equivalents. Irradiation doses as a percentage of the prescription dose (from the treatment planning system) around the junction were a minimum of 93–105%, a mean of 99–112%, and a maximum of 105–120%. Quality assurance (QA) was assessed in the cranial and caudal irradiation fields using imaging plates. Acute adverse effects of Grade 3 were observed in one patient (hypoalbuminemia), and a late adverse effect of Grade 3 was observed in one patient (liver abscess). Child–Pugh class elevations were observed in four patients (A to B: 3; B to C: 1). Overall survival rates at 1 and 2 years were 55 and 14%, respectively, with a median overall survival of 13.6 months. No patients showed local recurrence. Patch-field PBT supported by substantial QA therefore is one of the treatment options for large HCC.

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers

PurposeThe purpose of this study is to investigate the dose distribution of proton beam therapy (PBT) using a concomitant boost technique for unresectable pancreatic cancers.Materials and methodsThis simulation study involved 36 patients with unresectable pancreatic cancer. The irradiation dose was set as 67.5 gray equivalent (GyE) with 25 fractions using concomitant boost technique. The irradiation dose was set as 50 GyE to cover the whole target and another posterior beam of 17.5 GyE was added to ensure that 10% isodose line was not delivered to the gastrointestinal (GI) tract. Dose distribution of the gross tumor volume and GI tract was examined.ResultsV55GyE, 60GyE, 65GyE were 80.8, 66.5, and 42.4%, respectively, and mean dose was 64.1 GyE in all patients. The distance from the GI tract showed significant difference in dose distribution (P = 0.002 in V55GyE, 0.0009 in V60GyE, 0.003 in V65GyE, and 0.02 in mean dose, respectively). Location, tumor diameter, or lymph nodes metastasis did not show any difference.ConclusionsWe found that irradiated dose is closely related to the distance from the GI tract. Clinically, this protocol is expected to have outstanding effects on local control of tumors compared to conventional PBT.

A surveillance study of intensity-modulated radiation therapy for postoperative cervical cancer in Japan

Intensity-modulated radiation therapy (IMRT) was recently introduced to the field of gynecologic malignancies; however, its value is not yet validated. A clinical trial is in preparation to investigate the efficacy and feasibility of IMRT for postoperative cervical cancer. The object of this study was to perform a surveillance study of IMRT for post-operative cervical cancer. A questionnaire regarding the precise methods of conducting IMRT was sent to six institutions that had already introduced IMRT for post-operative cervical cancer, and the data were analyzed. Half of the institutions used static IMRT and the others used volumetric-modulated arc therapy (VMAT). Most institutions used body-immobilizing devices for patient fixation. Most institutions instructed patients to fill their bladder before undergoing planning CT or daily treatment. While one institution inserted metallic markers and another one used radio-contrast–soaked gauze to visualize the vaginal cuff, the other institutions used nothing for vaginal cuff visualization. Most institutions defined the clinical target volumes according to the Japan Clinical Oncology Group or the Radiation Therapy Oncology Group guidelines. Only one institution used a prescribed dose based on 95% of the PTV (D95), while the rest used the mean dose (Dmean). This valuable information from six leading institutions will be utilized in a future prospective clinical trial.