Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Early-stage hypopharyngeal squamous cell carcinoma treated with radical radiotherapy at a uniform dose of 70 Gy in 35 fractions: a single-center study.

INTRODUCTION: Hypopharyngeal squamous cell carcinoma (HSCC) is often undetected until advanced stages, which contributes to poor survival rates. Recent advances in diagnostic techniques have enhanced the feasibility of early detection, and this study evaluated the efficacy and safety of radical radiotherapy that specifically targets early stage HSCC. METHODS: This retrospective cohort study consecutively analyzed patients with clinical stage I or II HSCC between December 2008 and February 2023. These patients underwent radical radiotherapy with a uniform dose of 70 Gy delivered in 35 fractions to the primary site, followed by elective nodal irradiation. We assessed clinical outcomes, including overall survival (OS), disease-free survival (DFS), and 5-year locoregional control (LRC). Multivariate analyses were performed to identify the independent prognostic factors for OS. RESULTS: The 5-year OS rate of the entire cohort was 80.7% (95% confidence interval [CI] = 66.5-89.4%), with no significant difference between patients with clinical stage I and II HSCC. Stratified by subsite, the 5-year OS for pyriform sinus, posterior pharyngeal wall, and postcricoid region were 81.6, 68.2, and 100%, respectively. The ECOG-Performance status (PS) was identified as an independent risk factor for OS (hazard ratio [HR] = 8.457; 95% CI 1.325-53.970; p = 0.024). DFS at 5 years was 66.4%, with local recurrence being the most frequent, and LRC rate at 5 years was 79.3%. Acute and late-phase toxicities were predominantly mild to moderate, with no grade 3 or higher toxicities reported. CONCLUSION: This study supports radical radiotherapy as an effective approach for optimal tumor control in patients with early stage HSCC. Despite the limitations of this study, including its retrospective design and single-center confinement, our results revealed the effectiveness and feasibility of radical radiotherapy in the management of early stage HSCC.

Relationship between hydrogel spacer distribution and dosimetric parameters in linear-accelerator-based stereotactic body radiotherapy for prostate cancer.

PURPOSE: To explore the potential of quantitative parameters of the hydrogel spacer distribution as predictors for separating the rectum from the planning target volume (PTV) in linear-accelerator-based stereotactic body radiotherapy (SBRT) for prostate cancer. METHODS: Fifty-five patients underwent insertion of a hydrogel spacer and were divided into groups 1 and 2 of the PTV separated from and overlapping with the rectum, respectively. Prescribed doses of 36.25-45 Gy in five fractions were delivered to the PTV. The spacer cover ratio (SCR) and hydrogel-implant quality score (HIQS) were calculated. RESULTS: Dosimetric and quantitative parameters of the hydrogel spacer distribution were compared between the two groups. For PTV, D99% in group 1 (n = 29) was significantly higher than that in group 2 (n = 26), and Dmax, D0.03cc, D1cc, and D10% for the rectum were significantly lower in group 1 than in group 2. The SCR for prostate (89.5 ± 12.2%) in group 1 was significantly higher (p < 0.05) than that in group 2 (74.7 ± 10.3%). In contrast, the HIQS values did not show a significant difference between the groups. An area under the curve of 0.822 (95% confidence interval, 0.708-0.936) for the SCR was obtained with a cutoff of 93.6%, sensitivity of 62.1%, and specificity of 100%. CONCLUSIONS: The SCR seems promising to predict the separation of the rectum from the PTV in linear-accelerator-based SBRT for prostate cancer.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

OBJECTIVE: To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. METHODS: We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. RESULTS: The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20-43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for <68 Gy (log-rank; P = 0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P = 0.0006). For T3 + 4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82 cm3 (area under the curve = 0.67) and 43% for ≥82 cm3 (P = 0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P = 0.0024). CONCLUSIONS: Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.

Cumulative Incidence and Clinical Risk Factors of Radiation Cystitis after Radiotherapy for Prostate Cancer.

OBJECTIVES: This study aimed to evaluate the cumulative incidence of overall and severe radiation cystitis following external beam radiation therapy for prostate cancer and investigate the clinical factors predictive of radiation cystitis. METHODS: This retrospective study comprised 246 patients who received external beam radiation therapy for localized or locally advanced prostate cancer between 2013 and 2016 in our institution. Of these, 189 received primary radiation therapy and 57 received adjuvant/salvage radiation therapy. Radiation cystitis was recorded using the Common Terminology Criteria for Adverse Events version 5.0 definition, and severe radiation cystitis was defined as grade 3 or higher. All medical records were reviewed to calculate the cumulative incidence of radiation cystitis. Univariate and multivariate Cox regression analyses were used to evaluate its association with clinicopathologic features. RESULTS: The median follow-up period after radiation therapy was 56 months (range 5-81). The 5-year cumulative incidence of radiation cystitis and severe radiation cystitis was 16.2% and 3.0%, respectively. Multivariate analyses identified radiation therapy in the adjuvant/salvage setting was the sole risk factor associated with the development of radiation cystitis (hazard ratio: 2.75, p = 0.02). CONCLUSIONS: Radiation therapy in the post-prostatectomy setting was associated with increased risk of radiation cystitis compared with radiotherapy as the primary treatment.

Esophageal cancer patients' survival after complete response to definitive chemoradiotherapy: a retrospective analysis.

BACKGROUND: Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow. METHODS: We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking. RESULTS: At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n = 58), regional lymph nodes (n = 36), or distant disease (n = 34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n = 22), endoscopic treatment (n = 23), and lymphadenectomy (n = 9) was 47.4%, 70.9%, and 33.3%, respectively. CONCLUSIONS: A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.

Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival.

BACKGROUND: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. METHODS: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. RESULTS: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2-3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival. CONCLUSIONS: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.

Efficacy of a hydrogel spacer in three-dimensional conformal radiation therapy for prostate cancer.

OBJECTIVES: We aimed to compare the dose constraints fulfillment rate of the three-dimensional conformal radiotherapy treatment plan before and after a hydrogel spacer insertion. METHODS: The planning computed tomography scans of 39 patients who received stereotactic body radiotherapy for prostate cancer were used. All patients inserted a hydrogel spacer and underwent computed tomography scans before and after spacer insertion. The three-dimensional conformal radiotherapy plans according to NCCN classification, low-, intermediate- and high-risk, were made for each patient. Clinical target volume included prostate and seminal vesicle 2 cm for high risk, prostate and seminal vesicle 1 cm for intermediate risk and prostate only for low risk. Three-dimensional conformal radiotherapy including a seven-field conformal technique with 76 Gy in 38 fractions. Dose constraints for rectum and bladder were V70 Gy ≤ 15%, V65 Gy ≤ 30% and V40 Gy ≤ 60%. RESULTS: Among 39 patients, 35 (90%), 19 (49%) and 13 (33%) and 38 (97%), 38 (97%) and 34 (87%) patients before and after the spacer insertion fulfilled rectum dose constraints for low-, intermediate- and high-risk plans, respectively. A hydrogel spacer significantly reduced rectum dose and improved the rectum dose constraints fulfillment rate in intermediate (P < 0.01) and high (P < 0.01), but no difference was found in low-risk plan (P = 0.25). On multivariate analysis, spacer use was associated with the higher rectum dose constraints fulfillment rate. CONCLUSIONS: A hydrogel spacer reduced rectum dose and improved the dose constraints fulfillment rate in three-dimensional conformal radiotherapy plan. Although IMRT is the standard treatment, 3D-CRT using a hydrogel spacer may be a treatment option.

Long-term outcomes of multimodal therapy combining definitive chemoradiotherapy and salvage surgery for T4 esophageal squamous cell carcinoma.

BACKGROUND: Survival outcomes of patients with cT4 esophageal squamous cell carcinoma (ESCC) remain extremely poor. We aimed to investigate long-term outcomes and identify prognostic factors in patients treated by definitive chemoradiotherapy (dCRT) alone or with dCRT plus salvage surgery (SALV) for cT4 ESCC. PATIENTS AND METHODS: In total, 73 patients completing dCRT were analyzed. Patients achieving clinical complete response (CR) received follow-up evaluations thereafter. For patients diagnosed with clinical partial response (PR), potentially curative SALV was generally performed. Possible prognostic factors included demographic data, tumor staging, blood chemistry profiles, and esophageal stenosis. RESULTS: The 1- and 3-year overall survival (OS) rates of the 73 patients were 67.1% and 40.8%, respectively. Twenty-one patients (29%) achieved clinical CR with dCRT alone. Among 35 patients (48%) with clinical PR, 31 underwent SALV and 4 opted for non-surgical treatments. In the dCRT-alone group (n = 42), patients with clinical CR-PR (n = 25) showed significantly better 3-year OS than those who responded poorly to dCRT (stable or progressive) (n = 17) (67.5% vs. 0%, P < 0.001). In the SALV group (n = 31), curative SALV (n = 22, 73%) provided significantly better 3-year OS than non-curative SALV (58.7% vs. 0%, P < 0.001). Multivariable analysis revealed stenosis before dCRT (P = 0.02) and pretreatment elevated CRP (P = 0.02) to be independently associated with poor outcomes. CONCLUSIONS: The multimodal treatment strategy combining dCRT and SALV is rational for treating cT4 ESCC patients. When curative resection is feasible, SALV can provide good long-term survival outcome for patients who responded to dCRT but did not achieve clinical CR with dCRT alone.

[Improvement in Image Quality of CBCT during Treatment by Cycle Generative Adversarial Network].

PURPOSE: Volumetric modulated arc therapy (VMAT) can acquire projection images during rotational irradiation, and cone-beam computed tomography (CBCT) images during VMAT delivery can be reconstructed. The poor quality of CBCT images prevents accurate recognition of organ position during the treatment. The purpose of this study was to improve the image quality of CBCT during the treatment by cycle generative adversarial network (CycleGAN). METHOD: Twenty patients with clinically localized prostate cancer were treated with VMAT, and projection images for intra-treatment CBCT (iCBCT) were acquired. Synthesis of PCT (SynPCT) with improved image quality by CycleGAN requires only unpaired and unaligned iCBCT and planning CT (PCT) images for training. We performed visual and quantitative evaluation to compare iCBCT, SynPCT and PCT deformable image registration (DIR) to confirm the clinical usefulness. RESULT: We demonstrated suitable CycleGAN networks and hyperparameters for SynPCT. The image quality of SynPCT improved visually and quantitatively while preserving anatomical structures of the original iCBCT. The undesirable deformation of PCT was reduced when SynPCT was used as its reference instead of iCBCT. CONCLUSION: We have performed image synthesis with preservation of organ position by CycleGAN for iCBCT and confirmed the clinical usefulness.

Combined intravitreal methotrexate and immunochemotherapy followed by reduced-dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular lymphoma.

Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy. Seventeen patients initiated and 16 completed the protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in 3. Four-year progression-free survival (PFS) was 74·9% and 4-year overall survival (OS) was 86·3%, with a median follow-up period of 48·9 months. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4-year PFS and OS was 72·7% and 88·9%, respectively. Although white matter abnormalities shown by MRI were significantly increased at 4 years after rdWBRT, only one patient developed mild cognitive impairment. The combination of intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for primary IOL showed a potential to reduce CNS relapse rate and improved 4-year PFS and OS without increase of cognitive dysfunction.

Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence.

BACKGROUND: The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness. PATIENTS AND METHODS: A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival. RESULTS: HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7-70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ・} 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008-0.6, p = 0.009). CONCLUSION: In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment.

Lung stereotactic radiotherapy for oligometastases: comparison of oligo-recurrence and sync-oligometastases.

BACKGROUND: Oligometastases can be divided into sync-oligometastases and oligo-recurrence. The difference is whether the primary site is uncontrolled or controlled. The goal of this multicenter study was to evaluate treatment outcomes and factors affecting survival after stereotactic body radiotherapy for pulmonary oligometastases. METHODS: The information after stereotactic body radiotherapy from January 2004 to April 2014 was retrospectively collected. Ninety-six patients (65 males, 31 females) were enrolled. Ten cases (10%) were sync-oligometastases, 79 cases (82%) were oligo-recurrences and 7 (7%) were unclassified oligometastases with <6 months of disease-free interval. The median disease-free interval between initial therapy and stereotactic body radiotherapy was 24 months. The median calculated biological effective dose was 105.6 Gy. RESULTS: The median follow-up period was 32 months for survivors. The 3-year overall survival and relapse-free survival rates were 53% and 32%, respectively. No Grade 5 toxicity occurred. The median overall survival was 23.9 months for sync-oligometastases and 66.6 months for oligo-recurrence (P = 0.0029). On multivariate analysis, sync-oligometastases and multiple oligometastatic tumors were significant unfavorable factors for both overall survival and relapse-free survival. CONCLUSIONS: In stereotactic body radiotherapy for oligometastatic lung tumors, the state of oligo-recurrence has the potential of a significant prognostic factor for survival.

Evaluation of In Vivo Volumetric Dosimetry for Prostate Cancer Using Electronic Portal Imaging Device.

PURPOSE: Volumetric modulated arc therapy (VMAT) is capable of acquiring projection images using electronic portal imaging device (EPID). Commercial EPID-based dosimetry software, dosimetry check (DC), allows in vivo dosimetry using projection images. The purpose of this study was to evaluate in vivo dosimetry for prostate cancer using VMAT. METHOD: VMAT plans were generated for eight patients with prostate cancer using treatment planning system (TPS), and patient quality assurances (QAs) were carried out with phantom. We analyzed five plans as phantom study and five plans as patient study. Projection images were acquired during VMAT delivery. DC converted acquired images into fluence images and used a pencil beam algorithm to calculate dose distributions delivered on the CT images of the phantom and the patients. We evaluated isocenter point doses and gamma analysis in both studies and dose indexes of planning target volume (PTV), bladder and rectum in patient study. RESULTS AND DISCUSSION: Dose differences at the isocenter were less than a criterion in both studies. Pass rates of the gamma analysis were less than a criterion by two plans in the phantom study. Dose indexes of reconstructed distribution were lower than original plans and standard deviations of PTV in reconstructed distribution were larger than original plans. The errors were caused by some issues, such as the commissioning of DC, variations in patient anatomy, and patient positioning. CONCLUSION: The method was feasible to non-invasively perform in vivo dose evaluation for prostate cancer using VMAT.

[Evaluation of a Post-analysis Method for Cumulative Dose Distribution in Stereotactic Body Radiotherapy].

PURPOSE: The purpose of this study was to evaluate a post-analysis method for cumulative dose distribution in stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT) . METHOD: VMAT is capable of acquiring respiratory signals derived from projection images and machine parameters based on machine logs during VMAT delivery. Dose distributions were reconstructed from the respiratory signals and machine parameters in the condition where respiratory signals were without division, divided into 4 and 10 phases. The dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4DCT). Summation of the dose distributions was carried out using deformable image registration (DIR), and cumulative dose distributions were compared with those of the corresponding plans. RESULTS AND DISCUSSION: Without division, dose differences between cumulative distribution and plan were not significant. In the condition where respiratory signals were divided, dose differences were observed over dose in cranial region and under dose in caudal region of planning target volume (PTV). Differences between 4 and 10 phases were not significant. CONCLUSION: The present method was feasible for evaluating cumulative dose distribution in VMAT-SBRT using 4DCT and DIR.

A prospective nonrandomized phase I/II study of carbon ion radiotherapy in a favorable subset of locally advanced non-small cell lung cancer (NSCLC).

BACKGROUND: Although concurrent chemoradiotherapy (CCRT) has become the standard approach for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), most patients are not candidates for this treatment because of comorbidities. We evaluated the safety and efficacy of carbon ion radiotherapy (CIRT) in LA-NSCLC patients. METHODS: Patients with stage IIA to IIIA (UICC 7th edition) LA-NSCLC were enrolled in a sequential phase I/II trial. For a phase I dose escalation study, the total prescribed dose was increased by 4 Gray equivalents (GyE) in 2 steps, from 68 to 72 GyE and then to 76 GyE, using 16 fractions over 4 weeks. After determining the recommended dose, the phase II trial was started in an expanded cohort. RESULTS: Of the 36 patients treated in phase I, 2 grade 3 adverse events (radiation pneumonitis and tracheoesophageal fistula) were observed in the 76 GyE group. Accordingly, for phase II, the next consecutive 26 patients were treated with 72 GyE, with no grade 3 to 5 toxicities resulting. A total of 62 eligible patients were recruited. The majority of patients (49 of 62) were N0 or N1 patients, and the rest (13 of 62) were single-station N2 patients. The median follow-up period was 25.2 months. The 2-year local control rate (LCR) and overall survival (OS) for the entire cohort were 93.1% and 51.9%, respectively. In particular, patients with cT3-4N0 had an excellent prognosis; the 2-year OS and LCR were 69.3% and 100%, respectively. CONCLUSIONS: Short-course CIRT monotherapy shows promise as an effective nonsurgical treatment for inoperable LA-NSCLC.

The importance of good death components among cancer patients, the general population, oncologists, and oncology nurses in Japan: patients prefer "fighting against cancer".

BACKGROUND: The objectives of this study were to compare the importance of components of a good death among cancer patients, the general population, oncologists, and oncology nurses, and explore which patients preferred "fighting against cancer." METHODS: We conducted a cross-sectional anonymous self-reported survey of cancer patients who visited a radiation oncology outpatient clinic, oncologists, and oncology nurses at the Tokyo University Hospital and a random sample of the general population in the Tokyo metropolitan area. The outcomes were 18 previously developed components of a good death in Japanese cancer care consisting of 57 attributes. RESULTS: Three hundred ten patients, 353 subjects from the general population, 109 oncologists, and 366 oncology nurses participated. The desire to "fight against cancer" was highly significantly different between patients and oncologists (effect size [ES] = -1.40; P = 0.001) and patients and oncology nurses (ES = -1.12; P = 0.001). "Physical and cognitive control" was, similarly, highly significantly different between patients and oncologists (ES = -1.30; P = 0.001) and patients and oncology nurses (ES = -1.06; P = 0.001). Patients who emphasized "maintaining hope and pleasure" (P = 0.0001), "unawareness of death" (P = 0.0001), and "good relationship with family" (P = 0.004) favored "fighting against cancer." The patients, however, who emphasized "physical and psychological comfort" did not significantly favor "fighting against cancer" (P = 0.004). CONCLUSION: The importance of good death components differed between groups. Medical professionals should be aware of the diversity of values surrounding death and assess the patient's values and discuss them to support his or her quality of life. In addition, the development of care and a medical/social system to maintain hope and pleasure after failure of anticancer treatment is necessary.

Longitudinal assessments of quality of life and late toxicities before and after definitive chemoradiation for esophageal cancer.

OBJECTIVE: Definitive chemoradiotherapy is often considered for locally advanced esophageal cancer. We studied the effect of chemoradiotherapy treatment on patients' quality of life and late toxicities. METHODS: Patients undergoing definitive 5-fluorouracil and cis-diammine-glycolatoplatinum (nedaplatin) therapy concurrent with radiotherapy for esophageal cancer without operation adaptation completed standardized quality-of-life questionnaires before and after chemoradiotherapy and at regular times up to ∼5 years. We analyzed differences in a generic quality-of-life score questionnaire (Functional Assessment of Cancer Therapy-Esophageal scoring) over time by using a linear mixed-effects model. RESULTS: Longitudinal changes before the start of treatment were able to be evaluated in a total of 80 patients. The quality-of-life score before treatment was worse in patients with advanced stages than those with early stages. The quality-of-life score deteriorated once at the time of 2 or 3 months after starting chemoradiotherapy compared with pre-chemoradiotherapy and recovered and rose higher at 4 or 5 months than before starting chemoradiotherapy. After that, the recovery of quality of life was maintained up to the observation end. The score of physical functioning such as fatigue, nausea/vomiting, pain and dyspnea deteriorated at the time of 2 or 3 months after starting chemoradiotherapy compared with before chemoradiotherapy (80, 86, 94 and 89%). CONCLUSIONS: The quality-of-life score deteriorates once from before treatment due to acute complications by chemoradiotherapy, but recovers at 4 or 5 months and becomes better than before treatment.

Successful Control of Carcinoma of Unknown Primary with Axitinib, a Novel Molecular-Targeted Agent: A Case Report.

Carcinoma of unknown primary (CUP) is a common malignancy. In view of the poor prognosis of CUP, more effective therapy is needed. A 47-year-old man with CUP affecting the bone visited our institution. Treatment with heavy ion radiotherapy, cytotoxic chemotherapy, and resection of the bone tumor conferred neither control of the tumor nor the patient's symptoms such as tumor fever and bone pain. The bone biopsy at hemipelvectomy suggested undifferentiated adenocarcinoma with some features of clear cell carcinoma, although no lesions were detected in the kidneys. Based on the pathological diagnosis, treatment with sunitinib or everolimus was administered but resulted in progressive disease. However, axitinib showed favorable effects, controlling tumor progression and palliating his symptoms. To our knowledge, this is the first case of successful control of CUP with axitinib.

[Dose reconstruction using respiratory signals and machine parameters during treatment in stereotactic body radiotherapy].

PURPOSE: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. The purpose of this study was to reconstruct the dose distribution from respiratory signals and machine parameters acquired during stereotactic body radiotherapy (SBRT). METHODS: The treatment plans created for VMAT-SBRT included the constraint of 1 mm/degree in multileaf collimator (MLC) for a moving phantom and three patients with lung tumors. The respiratory signals were derived from projection images acquired during VMAT delivery, while the machine parameters were derived from machine logs. The respiratory signals and machine parameters were then linked along with the gantry angle. With this data, the dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4D CT). The doses at the isocenter, the point of max dose and the centroid of the target were compared with those of the corresponding plans. RESULTS AND DISCUSSION: In the phantom study, the maximum dose difference between the plan and "in-treatment" results was -0.4% at the centroid of the target. In the patient study, the difference was -1.8 ± 0.4% at the centroid of the target. Dose differences of the evaluated points between 4 and 10 phases were not significant. CONCLUSION: The present method successfully reconstructed the dose distribution using the respiratory signals and machine parameters acquired during treatment. This is a feasible method for verifying the actual dose for a moving target.