Protocol of a phase II study to evaluate the efficacy and safety of deep-inspiration breath-hold daily online adaptive radiotherapy for centrally located lung tumours (PUDDING study).

BACKGROUND: Centrally located lung tumours present a challenge because of their tendency to exhibit symptoms such as airway obstruction, atelectasis, and bleeding. Surgical resection of these tumours often requires sacrificing the lungs, making definitive radiotherapy the preferred alternative to avoid pneumonectomy. However, the proximity of these tumours to mediastinal organs at risk increases the potential for severe adverse events. To mitigate this risk, we propose a dual-method approach: deep inspiration breath-hold (DIBH) radiotherapy combined with adaptive radiotherapy. The aim of this single-centre, single-arm phase II study is to investigate the efficacy and safety of DIBH daily online adaptive radiotherapy. METHODS: Patients diagnosed with centrally located lung tumours according to the International Association for the Study of Lung Cancer recommendations, are enrolled and subjected to DIBH daily online adaptive radiotherapy. The primary endpoint is the one-year cumulative incidence of grade 3 or more severe adverse events, as classified by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). DISCUSSION: Delivering definitive radiotherapy for centrally located lung tumours presents a dilemma between ensuring optimal dose coverage for the planning target volume and the associated increased risk of adverse events. DIBH provides measurable dosimetric benefits by increasing the normal lung volume and distancing the tumour from critical mediastinal organs at risk, leading to reduced toxicity. DIBH adaptive radiotherapy has been proposed as an adjunct treatment option for abdominal and pelvic cancers. If the application of DIBH adaptive radiotherapy to centrally located lung tumours proves successful, this approach could shape future phase III trials and offer novel perspectives in lung tumour radiotherapy. TRIAL REGISTRATION: Registered at the Japan Registry of Clinical Trials (jRCT; https://jrct.niph.go.jp/ ); registration number: jRCT1052230085 ( https://jrct.niph.go.jp/en-latest-detail/jRCT1052230085 ).

Preoperative difficulty assessment of interval laparoscopic cholecystectomy for gallstones.

BACKGROUND: Laparoscopic cholecystectomy is the gold standard treatment for benign gallbladder disease. However, few studies have reported the difficulty of interval cholecystectomy after cholecystitis because early cholecystectomy is recommended for acute cholecystitis. In this study, we evaluated the difficulties associated with interval cholecystectomy for cholecystitis with gallstones. METHODS: We retrospectively analyzed patients with gallstones who underwent interval laparoscopic cholecystectomy for cholecystitis at our institution between January 2012 and December 2021. Patients were classified into laparoscopic total cholecystectomy and bailout procedure groups depending on whether they were converted to a bailout procedure, and their characteristics and outcomes were subsequently compared. Additionally, a logistic regression analysis of the preoperative factors contributing to bailout procedure conversion was performed. RESULTS: Of the 269 participants, 39 converted to bailout procedure, and bile duct injury occurred in one case (0.4%). In patient characteristics comparison, patients in the bailout procedure group were significantly older, had more impacted stones, had higher post-treatment choledocholithiasis, had severe cholecystitis, and had a higher rate of percutaneous transhepatic gallbladder drainage. There were no differences in the bile duct injury or perioperative complications between the two groups. In logistic regression multivariate analysis of the factors contributing to the bailout procedure, post-treatment of choledocholithiasis (P < .001), impacted stone (P = .002), and age ≥71 (P = .007) were independent risk factors. CONCLUSION: Impacted stones and choledocholithiasis are risk factors for conversion to bailout procedure and high difficulty in interval cholecystectomy. For such patients, interval cholecystectomy should be performed cautiously.

Applicability evaluation of the TRS-483 protocol for the determination of small-field output factors using different multi-leaf collimator and field-shaping types.

PURPOSE: To evaluate the applicability of TRS-483 output correction factors (CFs) for small-field output factors (OFs) using different multi-leaf collimators (MLC) and field-shaping types. METHODS: All measurements were performed on TrueBeam, TrueBeam STx, and Halcyon using 6 MV flattening filter-free energy. Four detectors, including CC01, CC04, microDiamond, and EDGE, were used. Nominal field sizes ranging from 1 × 1 to 4 × 4, and 10 × 10 cm2 were used to measure small-field OFs at source-to-axis distance of 100 cm with a 0° gantry angle in a 3D water phantom. Further, the field-shaping types were defined using jaw collimator or MLC (five different configurations). A field size of 10 × 10 cm2 was used as the reference for calculation of OFs obtained as ratio of detector readings (OFdet). The percentage difference and coefficient of variation of OFdet and OFdet corrected by applying CF were compared for each field size and configuration. RESULTS: For OFdet corrected by applying CF, the ranges of percentage difference and coefficient of variation in all configurations for ≥ 2 × 2 cm2 fields were reduced from 1.2-2.2 to 0.8-1.3 percentage points (%pt) and from 0.5-1.0 to 0.4-0.7%, respectively. For 1 × 1 cm2 field, the ranges of percentage difference and coefficient of variation were reduced from 3.3-5.7 to 1.2-2.2 %pt and from 2.2-3.7 to 0.8-1.1%, respectively. CONCLUSIONS: The CFs described in TRS-483 dosimetry protocol have broad applicability in reducing OF variations between detectors under different MLC and field-shaping types.

[Questionnaire Survey of Hands-on Seminar Using a Web Conferencing System in the COVID-19 Pandemic].

The purpose of this study was to evaluate the effectiveness of a hands-on seminar using a Web conferencing system, based on the post-event questionnaires of the face-to-face and online seminars of the hands-on seminar. For participants to feel realistic training in the online seminars, four educational videos explaining the procedure of the practical skill were created. We compared results of questionnaires acquired from participants after the face-to-face and online seminars. The questions about expectation, comprehension, satisfaction level, and lecture time for the seminars were graded on a 5-point scale. The higher the scores, the higher the rating, except for lecture time. A score of 3 was appropriate for the lecture time, with a higher score indicating that the seminar felt longer and a lower score indicating that the seminar felt shorter. In the evaluation of classroom lectures, such as expectation, comprehension, and satisfaction level for the seminars, there were no significant differences between the face-to-face and online seminars, and both achieved high scores of 4 or more. There was a significant difference in the evaluation of lecture time for classroom lectures, with participants feeling that it was too short in the face-to-face but just right in the online. In all evaluations for hands-on training and discussion, there were no significant differences between the face-to-face and online seminars, and both achieved high scores of 4 or more and time was short. It was concluded that our proposed online seminar approach could achieve a high level of evaluation as face-to-face seminars.

Recurrent Primary Abdominal Wall Abscess: A Case Report and Review of the Literature.

Primary abdominal wall abscess is extremely rare and difficult to diagnose because abdominal wall abscesses usually occur secondary to malignant tumors or inflammatory diseases. We experienced a case of an 80-year-old man with an asynchronous primary abdominal wall abscess with recurrence. Both abscesses were successfully treated with surgical drainage. A patient without any history of cancer or trauma presented to our department with right upper abdominal pain. His laboratory data showed an abnormal high inflammatory response, and computed tomography revealed a 40 × 30 mm mass formed in the rectus abdominis muscle of the upper right abdomen. The mass had no continuity with the surgical scar after cholecystectomy or intra-abdominal organs. Citrobacter diversus was detected in the culture from the mass and any epithelial components were not detected by biopsy. For the diagnosis of primary abdominal wall abscess, the patient underwent surgical drainage because antibiotic treatment was ineffective. The abscess disappeared promptly after the drainage. Thirteen months after the first treatment, another primary abdominal wall abscess was noted in the lower right abdomen. The abscess also promptly disappeared with surgical drainage. Primary abdominal wall abscess is difficult to diagnose because of its rarity. Prompt diagnosis and drainage are important to prevent exacerbation.

New patient setup procedure using surface-guided imaging to reduce body touch and skin marks in whole-breast irradiation during the COVID-19 pandemic.

This study aimed to assess the effectiveness of a new patient-setup procedure using surface-guided imaging during the coronavirus disease 2019 (COVID-19) pandemic for left-sided whole-breast irradiation with deep inspiration breath-hold. Two setup procedures were compared regarding patient positioning accuracy for the first 22 patients. The first was a traditional setup (T-setup) procedure that used a surface-guided system after patient setup with traditional skin marks and lasers. The second procedure involved a new setup (N-setup) that used only a surface-guided system. The positioning accuracy of the remaining 23 patients was assessed using a setup that combined marker reduction and the N-setup procedure. No significant difference was observed in positioning accuracy between the two setups. The positioning accuracy of the marker-reduction setup was within 3 mm in all directions. The N-setup procedure may be a useful strategy for preventing infection during or after the COVID-19 pandemic.

Usefulness of Preoperative Predictors of Pathological Complicated Appendicitis.

INTRODUCTION: Complicated appendicitis (CA) is often indicated for emergency surgery; however, preoperative predictors of pathological CA (pCA) remain unclear. Furthermore, characteristics of CA that can be treated conservatively have not yet been established. METHODS: 305 consecutive patients diagnosed with acute appendicitis were reviewed. The patients were divided into two groups: an emergency surgery and a conservative treatment group. The emergency surgery group was pathologically classified as having uncomplicated appendicitis (pUA) and pCA, and the preoperative predictors of pCA were retrospectively assessed. Based on the preoperative pCA predictors, a predictive nomogram whether conservative treatment would be successful or not was created. The predictors were applied to the conservative treatment group, and the outcomes were investigated. RESULTS: In the multiple logistic regression analysis of the factors contributing to pCA, C-reactive protein ≥3.5 mg/dL, ascites, appendiceal wall defect, and periappendiceal fluid collection were independent risk factors. Over 90% of cases without any of the above four preoperative pCA predictors were pUA. The accuracy of the nomogram was 0.938. CONCLUSION: Our preoperative predictors and nomogram are useful to aid in distinguishing pCA and pUA and to predict whether or not conservative treatment will be successful. Some CA can be treated with conservative treatment.

Therapeutic strategy for acute appendicitis based on laparoscopic surgery.

PURPOSE: The treatment strategies for acute appendicitis differ depending on the facility, and various studies have investigated the usefulness of conservative treatment with antibiotics, laparoscopic surgery, and interval appendectomy (IA). However, although laparoscopic surgery is widely used, the clinical strategy for acute appendicitis, especially complicated cases, remains controversial. We assessed a laparoscopic surgery-based treatment strategy for all patients diagnosed with appendicitis, including those with complicated appendicitis (CA). METHODS: We retrospectively analysed patients with acute appendicitis treated in our institution between January 2013 and December 2021. Patients were classified into uncomplicated appendicitis (UA) and CA groups based on computed tomography (CT) findings on the first visit, and the treatment course was subsequently compared. RESULTS: Of 305 participants, 218 were diagnosed with UA and 87 with CA, with surgery performed in 159 cases. Laparoscopic surgery was attempted in 153 cases and had a completion rate of 94.8% (145/153). All open laparotomy transition cases (n = 8) were emergency CA surgery cases. No significant differences were found in the incidence of postoperative complications in successful emergency laparoscopic surgeries. In univariate and multivariate analyses for the conversion to open laparotomy in CA, only the number of days from onset to surgery ≥ 6 days was an independent risk factor (odds ratio: 11.80; P < 0.01). CONCLUSION: Laparoscopic surgery is preferred in all appendicitis cases, including CA. Since laparoscopic surgery is difficult for CA when several days from the onset have passed, it is necessary that surgeons make an early decision on whether to operate.

Analyses of integrated EPID images for on-treatment quality assurance to account for interfractional variations in volumetric modulated arc therapy.

PURPOSE: To investigate the effects of interfractional variation, such as anatomical changes and setup errors, on dose delivery during treatment for prostate cancer (PC) and head and neck cancer (HNC) by courses of volumetric modulated arc therapy (VMAT) aided by on-treatment electronic portal imaging device (EPID) images. METHODS: Seven patients with PC and 20 patients with HNC who had received VMAT participated in this study. After obtaining photon fluence at the position of the EPID for each treatment arc from on-treatment integrated EPID images, we calculated the differences between the fluence for the first fraction and each subsequent fraction for each arc. The passing rates were investigated based on a tolerance level of 3% of the maximum fluence during the treatment courses and the correlations between the passing rates and anatomical changes. RESULTS: In PC, the median and lowest passing rates were 99.8% and 95.2%, respectively. No correlations between passing rates and interfractional variation were found. In HNC, the median passing rate of all fractions was 93.0%, and the lowest passing rate was 79.6% during the 35th fraction. Spearman's correlation coefficients between the passing rates and changes in weight or neck volume were - 0.77 and - 0.74, respectively. CONCLUSIONS: Analyses of the on-treatment EPID images facilitates estimates of the interfractional anatomical variation in HNC patients during VMAT and thus improves assessments of the need for re-planning or adaptive strategies and the timing thereof.

[Incident Analysis in Radiography Focusing on the Experience Period of Radiological Technologist].

We investigated the causes and trends of incidents related to radiography. From April 2014 to March 2016, 384 incident reports related to radiography were posted. We analyzed based on the nature of the incidents and the experience period of radiological technologist (RT). The types of incidents were 'Incorrect examination order by medical doctor' (50.0%), 'X-ray retake' (24%), 'Incorrect examination procedure' (9.9%), 'Fall or injury of the patient under examination' (3.6%), 'selection error of X-ray detector' (3.1%), 'patient mismatch' (1.8%), 'overdose' (1.3%), and 'others' (a malfunctioning device, trouble of systems and the other) (6.5%). There was no relationship between the number of incidents per person and the experience period as RT; (7.8/person for <3 years of experience, 9.7/person for 3-10 years, 6.4/person for 11-25 years of experience, 7.4/person for <25 years of experience). The experience period as RT are related to some types of incident reduction. 'Fall or injury of the patient under examination' and 'overdose' were more frequently reported by RTs of shorter experience (<3 years and 3-10 years of experience) than RTs of longer experience (11-25 years and <25 of experience). On the other hand, 'patient mismatch' and 'selection error of X-ray detector' were more frequently reported by RTs of long experience than RTs of short experience.

RT-qPCR analysis of the tumor antigens TOMM34 and RNF43 in samples extracted from paraffin-embedded specimens of colorectal cancer.

Comprehensive genetic analysis of colorectal malignant tumors by microarrays has identified translocase of the outer mitochondrial membrane 34 (TOMM34) and ring finger protein 43 (RNF43) as highly expressed oncogenes in malignant colorectal tumors. Vaccine therapy using cancer peptides synthesized using the amino acid sequences of tumor antigens is currently undergoing clinical trials. Since it is important to perform vaccine therapy based on the oncogene expression levels in individual tumors, analysis of tumor antigen expression is necessary for this therapy. However, the quality of the messenger RNA extracted from formalin-fixed and paraffin-embedded specimens is generally considered insufficient for gene quantification. The present study examined whether it could be possible to quantify the expression of TOMM34 and RNF43 in colorectal cancer and liver metastasis samples prepared from paraffin blocks. The formalin-fixed and paraffin-embedded specimens were sliced for slides and the colorectal cancer and normal mucosal tissues were obtained from the slides. Total RNA was extracted from the tissue samples, and quantitative polymerase chain reaction (qPCR) was performed using the Universal ProbeLibrary as a PCR probe. Quantification of TOMM34 and RNF43 gene expression in several-year-old paraffin-embedded colorectal cancer specimens was possible by qPCR using the Universal ProbeLibrary. qPCR revealed that TOMM34 expression was elevated in 78.9% (15 of 19 cases) of the primary tumors and in 73.7% (14 of 19 cases) of the liver metastasis samples. RNF43 expression was elevated in 63.2% (12 of 19 cases) of the primary tumors and in 73.7% (14 of 19 cases) of the liver metastasis samples.

Investigation of interfractional shape variations based on statistical point distribution model for prostate cancer radiation therapy.

PURPOSE: The setup errors and organ motion errors pertaining to clinical target volume (CTV) have been considered as two major causes of uncertainties in the determination of the CTV-to-planning target volume (PTV) margins for prostate cancer radiation treatment planning. We based our study on the assumption that interfractional target shape variations are not negligible as another source of uncertainty for the determination of precise CTV-to-PTV margins. Thus, we investigated the interfractional shape variations of CTVs based on a point distribution model (PDM) for prostate cancer radiation therapy. MATERIALS AND METHODS: To quantitate the shape variations of CTVs, the PDM was applied for the contours of 4 types of CTV regions (low-risk, intermediate- risk, high-risk CTVs, and prostate plus entire seminal vesicles), which were delineated by considering prostate cancer risk groups on planning computed tomography (CT) and cone beam CT (CBCT) images of 73 fractions of 10 patients. The standard deviations (SDs) of the interfractional random errors for shape variations were obtained from covariance matrices based on the PDMs, which were generated from vertices of triangulated CTV surfaces. The correspondences between CTV surface vertices were determined based on a thin-plate spline robust point matching algorithm. The systematic error for shape variations was defined as the average deviation between surfaces of an average CTV and planning CTVs, and the random error as the average deviation of CTV surface vertices for fractions from an average CTV surface. RESULTS: The means of the SDs of the systematic errors for the four types of CTVs ranged from 1.0 to 2.0 mm along the anterior direction, 1.2 to 2.6 mm along the posterior direction, 1.0 to 2.5 mm along the superior direction, 0.9 to 1.9 mm along the inferior direction, 0.9 to 2.6 mm along the right direction, and 1.0 to 3.0 mm along the left direction. Concerning the random errors, the means of the SDs ranged from 0.9 to 1.2 mm along the anterior direction, 1.0 to 1.4 mm along the posterior direction, 0.9 to 1.3 mm along the superior direction, 0.8 to 1.0 mm along the inferior direction, 0.8 to 0.9 mm along the right direction, and 0.8 to 1.0 mm along the left direction. CONCLUSIONS: Since the shape variations were not negligible for intermediate and high-risk CTVs, they should be taken into account for the determination of the CTV-to-PTV margins in radiation treatment planning of prostate cancer.

Fever-range whole-body heat treatment stimulates antigen-specific T-cell responses in humans.

Increase in body temperature has been thought to play an important role in the regulation of immune responses, although its precise mechanisms are still under investigation. Here, we examined the effects of physiologically relevant thermal stress on the cytokine production from human peripheral T cells. Volunteers were heated using a whole-body hyperthermia device, the rectal temperature was maintained above 38.5 °C for more than 60 min, and peripheral blood mononuclear cells (PBMCs) were obtained before and after the treatment. When T cells were stimulated with anti-CD3/CD28 antibodies, marked increases in the production of interferon-γ (IFN-γ) and interleukin-2 were observed in PBMCs prepared immediately after and 24h after the treatment. Similarly, enhanced production of IFN-γ in response to the tuberculin purified protein derivative or antigenic viral peptides was also observed immediately after and 24h after the treatment. Fluorescence photo-bleaching analyses showed heat-induced increase of membrane fluidity in T cells, which probably enables them to induce rapid and efficient cluster formation of molecules involved in antigen recognition and signal transduction for T-cell stimulation. We concluded that physiologically relevant thermal stress could efficiently modify T-cell responsiveness to various stimuli, including enhanced responses to specific antigens.

[Establishment of induced pluripotent stem cells from adipose tissue-derived stem cells for dendritic cell-based cancer vaccines].

Recently, studies on regenerative stem cell therapy are being encouraged, and efforts to generate dendritic cells, which play important roles in cancer immunotherapy, from stem cells are being made in the field of tumor immunology. Therapeutic acquisition of stem cells has important clinical applications. Studies on induced pluripotent stem(iPS)cells generated from somatic cells with pluripotent genes have advanced in recent years. Stem cells are reported to be found in adipose tissue (adipose-derived stem cells, ADSC). Our goal is to develop a new cancer vaccine by using dendritic cells generated from ADSC. In a preliminary study, we examined whether iPS cells can be generated from ADSC to serve as a source of dendritic cells.We introduced a plasmid with pluripotent genes(OCT3/4, KLF4, SOX2, L-MYC, LIN28, p53-shRNA)into an ADSC strain derived from adipose tissue by electroporation and subsequently cultured the cells for further examination. A colony sugges- tive of iPS cells from ADSC was observed. OCT3/4, KLF4, SOX2, L-MYC, and LIN28 mRNAs were expressed in the cultured cells, as confirmed by reverse transcriptase-polymerase chain reaction(RT-PCR). On the basis of these results, we confirmed that iPS cells were generated from ADSC. The method of inducing dendritic cells from iPS cells has already been reported, and the results of this study suggest that ADSC is a potential source of dendritic cells.

Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer.

BACKGROUND: The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and only a few standard treatments are available for this condition. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with three peptides derived from cancer-testis antigens. METHODS: This study was conducted as a phase I trial. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. Three HLA-A*2402 restricted epitope peptides-cell division cycle associated 1 (CDCA1), cadherin 3 (CDH3) and kinesin family member 20A (KIF20A)-were administered subcutaneously, and the adverse events and immune response were assessed. The clinical effects observed were the tumor response, progression-free survival (PFS) and overall survival (OS). RESULTS: The three-peptide vaccination was well-tolerated up to a dose of 3 mg per peptide (9 mg total). No grade 3 or 4 adverse events were observed after vaccination. Peptide-specific T cell immune responses were observed in all patients and stable disease was observed in 5 of 9 patients. The median PFS and OS were 3.4 and 9.7 months. The Grade 2 injection site reaction and continuous vaccination after PD judgment appeared to be prognostic of OS. CONCLUSIONS: Multiple-peptide vaccination was well tolerated and induced peptide-specific T-cell responses. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003229).

Examination of MARCO activity on dendritic cell phenotype and function using a gene knockout mouse.

We have reported the upregulation of MARCO, a member of the class A scavenger receptor family, on the surface of murine and human dendritic cells (DCs) pulsed with tumor lysates. Exposure of murine tumor lysate-pulsed DCs to an anti-MARCO antibody led to loss of dendritic-like processes and enhanced migratory capacity. In this study, we have further examined the biological and therapeutic implications of MARCO expression by DCs. DCs generated from the bone marrow (bm) of MARCO knockout (MARCO⁻/⁻) mice were phenotypically similar to DCs generated from the bm of wild-type mice and produced normal levels of IL-12 and TNF-α when exposed to LPS. MARCO⁻/⁻ DCs demonstrated enhanced migratory capacity in response to CCL-21 in vitro. After subcutaneous injection into mice, MARCO⁻/⁻ TP-DCs migrated more efficiently to the draining lymph node leading to enhanced generation of tumor-specific IFN-γ producing T cells and improved tumor regression and survival in B16 melanoma-bearing mice. These results support targeting MARCO on the surface of DCs to improve trafficking and induction of anti-tumor immunity.

Long-term Vaccination with Multiple Peptides Derived from Cancer-Testis Antigens Can Maintain a Specific T-cell Response and Achieve Disease Stability in Advanced Biliary Tract Cancer.

PURPOSE: The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and there are only a few standard treatments. We conducted a phase I trial to investigate the safety, immune response, and antitumor effect of vaccination with four peptides derived from cancer-testis antigens, with a focus on their fluctuations during long-term vaccination until the disease had progressed. EXPERIMENTAL DESIGN: Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. HLA-A*2402-restricted epitope peptides, lymphocyte antigen 6 complex locus K, TTK protein kinase, insulin-like growth factor-II mRNA-binding protein 3, and DEP domain containing 1 were vaccinated subcutaneously once a week at doses of 0.5, 1, or 2 mg and continued until disease progression. The adverse events were assessed by Common Terminology Criteria for Adverse Events and the immune response was monitored by an enzyme-linked immunospot assay or by flow cytometry. The clinical effects observed were tumor response, progression-free survival (PFS), and overall survival (OS). RESULTS: Four-peptide vaccination was well tolerated. No grade 3 or 4 adverse events were observed. Peptide-specific T-cell immune responses were observed in seven of nine patients and clinical responses were observed in six of nine patients. The median PFS and OS were 156 and 380 days. The injection site reaction and CTL induction seemed to be prognostic factors of both PFS and OS. CONCLUSIONS: Four-peptide vaccination was well tolerated and seemed to provide some clinical benefit to some patients. These immunologic and clinical responses were maintained over the long term through continuous vaccinations.

Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer.

Recently, analysis of tumor antigens using micro-arrays has revealed upregulation of cancer-testis antigens RNF43 and TOMM34 and vascular endothelial growth factor receptors VEGFR1 and VEGFR2 in colorectal cancer. A phase I clinical trial of peptide vaccine therapy together with oral anticancer drugs was conducted to treat advanced colorectal cancer using synthesized peptides of these tumor antigens in order to confirm the safety, immunogenicity and activity of this treatment. The subjects were patients with a human leukocyte antigen (HLA) type of A2402 who had inoperable colorectal cancer but had failed to respond to or were unable to undergo standard chemotherapy. Four peptides (RNF43, TOMM34, VEGFR1 and VEGFR2) were emulsified with incomplete Freund's adjuvant (Montanide), and the resulting solution was administered subcutaneously once a week. Patients received the oral anticancer drug tegafur-uracil plus leucovorin for four weeks continuously as part of one course followed by one week of rest. The primary endpoint of the trial was observation of adverse events as determined by the NCI-CTCAE criteria, and the secondary endpoints were the size of the tumor and the number of cytotoxic T lymphocytes (CTLs) in the peripheral blood after treatment. Vaccine therapy was administered 148 times to 10 patients from July 2008 to December 2009. The adverse events were grade 1 redness and induration, a grade 2 skin ulcer at the vaccination site and grade 1 pyrexia. All patients tolerated treatment. Tumor imaging revealed that after 1 course of treatment 1 patient had partial response (PR), 7 had stable disease (SD) and 2 had progressive disease. A CTL assay of 10 patients revealed an increase in peptide-specific CTLs in patients with PR and SD, and the clinical responses of those patients were observed. Kaplan­Meier analysis indicated that patients who had a strong CTL reaction had a tendency to have longer progression­free survival and overall survival.

Computerized estimation of patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy.

We have developed a computerized method for estimating patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy. The patient setup errors were estimated based on a template-matching technique that compared the portal image and a localized pelvic template image with a clinical target volume produced from a digitally reconstructed radiography (DRR) image of each patient. We evaluated the proposed method by calculating the residual error between the patient setup error obtained by the proposed method and the gold standard setup error determined by consensus between two radiation oncologists. Eleven training cases with prostate cancer were used for development of the proposed method, and then we applied the method to 10 test cases as a validation test. As a result, the residual errors in the anterior-posterior, superior-inferior and left-right directions were smaller than 2 mm for the validation test. The mean residual error was 2.65 ± 1.21 mm in the Euclidean distance for training cases, and 3.10 ± 1.49 mm for the validation test. There was no statistically significant difference in the residual error between the test for training cases and the validation test (P = 0.438). The proposed method appears to be robust for detecting patient setup error in the treatment of prostate cancer radiotherapy.