Stereotactic ablative body radiotherapy with a central high dose using CyberKnife for metastatic lung tumors.

BACKGROUND: The CyberKnife system features a robotically-positioned linear accelerator to deliver real-time image-guided stereotactic ablative body radiotherapy (SABR). It achieves steep dose gradients using irradiation from hundreds of different directions and increases the central dose of the gross tumor volume (GTV) without increasing the marginal dose to the planning target volume. We evaluated the effectiveness and safety of SABR with a central high dose using CyberKnife for metastatic lung tumors. METHODS: A total of 73 patients with 112 metastatic lung tumors treated with CyberKnife were retrospectively analyzed. Local control, progression-free survival, and overall survival were calculated using the Kaplan-Meier method. The median age was 69.2 years. The most common primary sites were the uterus (n = 34), colorectum (n = 24), head and neck (n = 17), and esophagus (n = 16). For peripheral lung tumors, the median radiation dose was 52 Gy in 4 fractions, whereas for centrally located lung tumors, it was 60 Gy in 8-10 fractions. The dose prescription was defined as 99% of the solid tumor components of the GTV. The median maximum dose within the GTV was 61.0 Gy. The GTV and planning target volume were enclosed conformally by the 80% and 70% isodose lines of the maximum dose, respectively. The median follow-up period was extended to 24.7 months; it was 33.0 months for survivors. RESULTS: The 2-year local control, progression-free survival, and overall survival rates were 89.1%, 37.1%, and 71.3%, respectively. Toxicities of grade ≥ 2 were noted as grade 2 and 3 radiation pneumonitis in one patient each. The two patients with grade 2 or higher radiation pneumonitis had both received simultaneous irradiation at two or three metastatic lung tumor sites. No toxicity of grade ≥ 2 was observed in patients with metastasis in one lung only. CONCLUSIONS: SABR with a central high dose using CyberKnife for metastatic lung tumors is effective with acceptable toxicity. TRIAL REGISTRATION: Number: 20557, Name: Stereotactic ablative radiotherapy using CyberKnife for metastatic lung tumor, URL: http://www.radonc.med.osaka-u.ac.jp/pdf/SBRT.pdf , Date of registration: April 1, 2021 (retrospectively registered), Date of enrollment: May 1, 2014.

Increased toxicities associated with dose escalation of stereotactic body radiation therapy in prostate cancer: results from a phase I/II study.

BACKGROUND: This dose-escalation study evaluated the toxicity and efficacy of different stereotactic body radiation therapy (SBRT) doses for selecting an optimal dose for prostatic adenocarcinoma (PCa). MATERIALS AND METHODS: This clinical trial was registered at UMIN (UMIN000014328). Patients with low- or intermediate-risk PCa were equally assigned to 3 SBRT dose levels: 35, 37.5, and 40 Gy per 5 fractions. The primary endpoint was the occurrence rate of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) adverse events at 2 years, while the secondary endpoint was the 2-year biochemical relapse-free (bRF) rate. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Seventy-five patients (median age, 70 years) were enrolled from March 2014 to January 2018, of whom 10 (15%) and 65 (85%) had low- and intermediate-risk PCa, respectively. The median follow-up time was 48 months. Twelve (16%) patients received neoadjuvant androgen deprivation therapy. The 2-year occurrence rates of grade 2 late GU and GI toxicities were 34 and 7% in all cohorts, respectively (35 Gy: 21 and 4%; 37.5 Gy: 40 and 14%; 40 Gy: 42 and 5%). The occurrence risk of GU toxicities significantly increased with dose escalation (p = 0.0256). Grades 2 and 3 acute GU toxicities were observed in 19 (25%) and 1 (1%), respectively. Grade 2 acute GI toxicity was observed in 8 (11%) patients. No grade ≥3 GI or ≥4 GU acute toxicity or grade ≥3 late toxicity was observed. Clinical recurrence was detected in 2 patients. CONCLUSIONS: An SBRT dose of 35 Gy per 5 fractions is less likely to cause adverse events in patients with PCa than 375- and 40-Gy SBRT doses. Higher doses of SBRT should be applied with caution.

Circulating tumor HPV DNA complements PET-CT in guiding management after radiotherapy in HPV-related squamous cell carcinoma of the head and neck.

Positron emission tomography and computed tomography (PET-CT) is widely used to assess the response to radiotherapy. However, the ability of PET-CT to predict treatment failure in human papillomavirus (HPV)-related squamous cell carcinoma of the head and neck (HNSCC) is unsatisfactory. We quantified circulating tumor HPV type16 DNA (ctHPV16DNA) using optimized droplet digital PCR in 35 patients with HPV16-related HNSCC, who received radiotherapy with or without chemotherapy, and prospectively correlated ctHPV16DNA and metabolic response with treatment failure. After a median follow-up of 21 months, ctHPV16DNA and PET-CT had similar negative predictive values (89.7% vs 84.0%), whereas the positive predictive value was much higher in ctHPV16DNA than in PET-CT (100% vs 50.0%). Notably, six patients who had detectable posttreatment ctHPV16DNA all had treatment failure irrespective of metabolic response, whereas none of five patients who had partial metabolic response without detectable posttreatment ctHPV16DNA had treatment failure. The risk of treatment failure was high in patients who had incomplete metabolic response with detectable posttreatment ctHPV16DNA (hazard ratio [HR], 138.8; 95% confidence interval [CI], 15.5-3366.4; P < .0001) and intermediate in patients who had discordant results between metabolic response and posttreatment ctHPV16DNA (HR, 4.7; 95% CI, 0.8-36.2, P = .09) as compared with patients who had complete metabolic response without detectable posttreatment ctHPV16DNA. One-year event-free survival rates of each risk group were 0%, 88% (95% CI, 46-98) and 95% (95% CI, 72-99), respectively (P < .0001). In conclusion, posttreatment ctHPV16DNA complements PET-CT and helps guide decisions managing patients with HPV16-related HNSCC after radiotherapy.

Monitoring expiratory carbon monoxide to study the effect of complete smoking cessation on definitive radiation therapy for early stage glottic carcinoma.

BACKGROUND: Previous studies reported that cigarette smoking during radiation therapy was associated with unfavorable outcomes in various cancers using medical interviewing or monitoring of cotinine. Here, we evaluated the effect of smoking cessation on definitive radiation therapy for early stage glottic carcinoma by monitoring expiratory carbon monoxide (CO). MATERIAL AND METHODS: We enrolled 103 patients with early glottic carcinoma (T1N0/T2N0 = 79/24) who underwent conventional radiotherapy between 2005 and 2016. The median age was 70 years. Pathologically, all patients had squamous cell carcinoma. Since 2009, we confirmed smoking cessation before radiation therapy by medical interviews. Since 2014, we measured expiratory CO to strictly monitor smoking cessation. The patients were divided according to diagnosis years: 'no cessation' (2005-2008), 'incomplete cessation' (2009-2013), and 'complete cessation' (2014-2016). We retrospectively analyzed the local recurrence rate and disease-free survival (DFS). RESULTS: The median follow-up period was 60.1 months (range, 1.9-110.0 months). The 2-year local recurrence rate in the 'complete cessation' group was 5.3% and tended to be lower than that in the 'incomplete cessation' group (13.7%) and 'no cessation' group (21.2%). Multivariate analysis revealed that 'no cessation' was a risk factor for DFS (hazard ratio [HR] = 4.25) and local recurrence rate (HR = 16.5, p < .05) compared to 'complete cessation.' DISCUSSION: We confirmed that the 'complete cessation' group had better prognosis than the 'no cessation' group by monitoring expiratory CO during radiation therapy for early stage glottic carcinoma. Moreover, monitoring expiratory CO was easier and more suitable than conventional methods for evaluating smoking cessation because it provided real-time measurements.

Local hyperthermia combined with CTLA-4 blockade induces both local and abscopal effects in a murine breast cancer model.

PURPOSE: To evaluate the antitumor efficacy in local and distant tumors induced by local hyperthermia with CTLA-4 blockade. METHODS: A mouse breast cancer cell line was inoculated into both sides of the legs of mice. The mice were treated with three administrations of CTLA-4 blockade, a single application of local hyperthermia (42.5 °C for 20 min) to the tumor on one side of the leg, or the combination of the two. Tumor growth in locally heated tumors (HT tumors) and unheated distant tumors (UnHT tumors) and overall survival were evaluated. RESULTS: In the combination group, tumor volume significantly decreased for both HT and UnHT tumors compared with the tumors in the untreated and local hyperthermia monotherapy groups. Remarkable efficacy was only observed in the combination therapy group, in which 7 of 18 mice responded to HT and UnHT tumors, with significant prolonged overall survival. CONCLUSIONS: Combination therapy enhanced the antitumor response not only in HT tumors but also in UnHT tumors and prolonged overall survival.

Impact of a reduction in follow-up frequency on life expectancy in uterine cervical cancer patients.

BACKGROUND: The appropriate interval of post-treatment follow-up appointments for uterine cervical cancer is unclear. The aim of this study was to investigate the impact of reducing the frequency of post-treatment follow-up examinations on life expectancy and medical expenses in cervical cancer patients. METHODS: Cervical cancer patients who were treated with radiotherapy between 2008 and 2017, underwent a less frequent follow-up program, and subsequently developed recurrent disease were included in consecutive group (CG). Non-randomized groups of cervical cancer patients who underwent a frequent follow-up program after radiotherapy between 1997 and 2007, and subsequently developed recurrent disease were also identified through a chart review and served as a comparison group (primary group [PG]). Clinical data regarding the primary disease, follow-up, recurrence, and survival were collected. Univariate and multivariate analyses of predictors of survival were performed. RESULTS: A total of 263 recurrent cervical cancer patients (PG: 154, CG: 109) were included in the current study. A reduction in follow-up frequency of up to 40% did not increase the frequency of symptomatic recurrence (PG: vs. CG: 31.2% vs. 35.8%, p = 0.43) or reduce the median overall survival periods of recurrent cervical cancer patients (PG vs. CG: 32 months vs. 36 months, p = 0.15). However, the reduction in the follow-up frequency significantly reduced follow-up costs. CONCLUSION: Reducing the frequency of follow-up by up to 40% did not result in shorter overall survival compared with a conventional follow-up program. The results of this study provide a rationale for future studies investigating the optimal follow-up schedule for patients with cervical cancer.

A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Neoadjuvant therapy reportedly shows only marginal clinical benefit in pancreatic ductal adenocarcinoma (PDAC), especially in resectable cases. However, with more effective regimens, neoadjuvant therapy may become a standard of care for resectable cases. A prospective, open-label, multicenter phases 1 and 2 trial of neoadjuvant therapy was conducted using full-dose gemcitabine and S-1 concurrently with 50.4 Gy of radiation therapy (GSRT) for resectable PDAC. This report describes the phase 2 results. METHODS: The phase 2 part of this study enrolled 57 patients with cytologically or histologically proven PDAC deemed resectable based on imaging before neoadjuvant therapy. These patients received GSRT. After reevaluation by computed tomography scan, surgical exploration was performed, followed by adjuvant therapy. According to the prescribed protocol of the clinical trial, statistical analyses included 57 phase 2 patients and 6 phase 1 patients who received the same dosage as in phase 2. RESULTS: This trial enrolled 63 patients (42 men and 21 women) with a median age of 70 years. Leukopenia or neutropenia of grade 3 or higher occurred for 79% of the patients, but no other severe adverse events were observed. Among the 63 patients, 54 underwent surgical resection. Intention-to-treat analysis of the 63 patients showed an excellent median survival time lasting as long as 55.3 months. The patients who completed neoadjuvant therapy, surgery, and adjuvant therapy had a 5-year survival rate of 56.6%. CONCLUSIONS: This regimen showed outstanding clinical efficacy with acceptable tolerability for patients with resectable PDAC.

The heart's exposure to radiation increases the risk of cardiac toxicity after chemoradiotherapy for superficial esophageal cancer: a retrospective cohort study.

BACKGROUND: Chemoradiotherapy effectively treats superficial esophageal cancer and is optimal to preserve organs. However, late toxicity, particularly in cardiac diseases, obstructs clinical outcomes. We revealed the risk factors for cardiac event development post-chemoradiotherapy. METHODS: Data from 80 patients who were diagnosed with submucosal invasive esophageal cancer without metastasis (confirmed using multiple modalities) and who underwent chemoradiotherapy between 2006 and 2014 were analyzed. Patients were 11% (9/80) female, and the median age and follow-up were 66.5 y and 73 mo, respectively. We calculated the individual radiation dose to the heart and analyzed relationships between the cardiac event occurrence rate and each clinical factor. RESULTS: The 5-y overall and recurrence-free survival rates were 74.6 and 62.4%, respectively. Among the total number of deaths, 34.6% was caused by esophageal cancer. During the follow-up, 13 patients developed severe cardiac events (ischemic heart diseases, n = 7; pericardial effusion, n = 3, atrial fibrillation, n = 1; and sudden death, n = 2). The significant risk factor for cardiac events post-chemoradiotherapy was the level of the heart's exposure to radiation, with higher exposure associated with greater occurrence. History of smoking, obesity, comorbidity, and history of cardiac disease were unrelated to cardiac event occurrence post-chemoradiotherapy. CONCLUSIONS: Chemoradiotherapy is a favorable intervention for superficial esophageal cancer. Reducing the radiation dose to the heart likely contributes to preventing cardiac toxicity post-chemoradiotherapy.

Single-arm confirmatory trial of postoperative concurrent chemoradiotherapy using intensity modulated radiation therapy for patients with high-risk uterine cervical cancer: Japan Clinical Oncology Group study (JCOG1402).

A single-arm multi-center confirmatory trial was started in Japan to confirm the efficacy and safety of post-radical hysterectomy concurrent chemoradiotherapy using intensity-modulated radiation therapy (IMRT-CCRT) for patients with high-risk uterine cervical cancer, for which the current standard treatment is CCRT using three-dimensional conformal radiation therapy (3DCRT-CCRT). This study began in April 2017 and a total of 220 patients will be accrued from 44 institutions within 3.5 years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are overall survival, loco-regional relapse-free survival, proportion of late lower gastrointestinal adverse events greater than or equal to grade 3, proportion of lower edema limbs, adverse events, and serious adverse events. This trial was registered at the Japan Registry of Clinical Trials as jRCTs031180194 (https://jrct.niph.go.jp/).

Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors.

BACKGROUND: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. METHODS: We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. RESULTS: The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. CONCLUSIONS: The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Radiotherapy for isolated recurrent epithelial ovarian cancer: A single institutional experience.

AIM: To evaluate the efficacy and toxicity of external beam radiotherapy (RT) for isolated recurrent epithelial ovarian cancer (EOC). METHODS: Twenty-four isolated recurrent EOC patients treated with RT at Osaka University Hospital between January 2000 and January 2017 were included in the current study. Data regarding the primary or recurrent diseases, follow-up findings, and efficacy or toxicities of RT were collected and retrospectively analyzed. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Their median age was 59 years. Most patients had International Federation of Gynecology and Obstetrics stage III-IV diseases at the initial diagnosis. Histologically, serous adenocarcinoma was predominant, followed by clear cell adenocarcinoma. All patients had received at least one regimen of platinum-based chemotherapy; 8 were platinum-sensitive relapse and the others were platinum-resistant. Lymph nodes were the most common sites of recurrence, and the median tumor size was 25.5 mm. The median total dose of RT administered was 54 Gy, with a median daily dose of 2 Gy. RT was well-tolerated, and no patients experienced Grade 3/4 toxicities. The in-field overall response rate was 58.3% (14/24), the median regression rate was -40.2% (range: -100 to 0) and the median survival period after RT was 17 months. The 1-year survival and local progression-free survival rates after RT were 66.7% and 45.8%, respectively. CONCLUSION: RT showed significant antitumor effect against isolated recurrent EOC without causing severe toxicities. Prospective studies with sufficient statistical power are warranted to further evaluate the role of RT in this patient population.

Feasibility of virtual starshot analysis providing submillimeter radiation isocenter accuracy: A long-term multi-institutional analysis.

PURPOSE: We developed a technique to calculate the offset between room lasers and the radiation isocenter using a digital Winston-Lutz (WL) test with a starshot technique. We have performed isocenter localization quality assurance (QA) with submillimeter accuracy for a long period. Here we evaluated the feasibility and accuracy of this virtual starshot (VS) analysis for isocenter localization QA. METHODS: A 6-MV photon beam with a square multileaf collimator field was used to irradiate a WL sphere positioned at the intersection of the room lasers. Images were acquired using an electronic portal imaging device. A four-field WL test was performed, and the path of each beam was calculated from the offset between the beam and sphere. Virtual starshot analysis was used to analyze the radiation isocenter, which calculates the center of the beam paths by using a least-squares method, similar to the starshot analysis. Then, eight coplanar and 12 noncoplanar beams were irradiated to evaluate isocenter localization accuracy. RESULTS: Several VS analyses, using different WL spheres, were performed at three institutions, and the calculated accuracies were within 0.1 mm at all institutions. Long-term analysis showed that the isocenter localization accuracy was appropriately managed with three-dimensional accuracy within ± 0.5 mm for 90 months after the first laser adjustments. The offset between each beam and the room laser was within 0.6 mm and within 1.0 mm for eight coplanar and 12 noncoplanar beams, respectively, for 90 months. Cone-beam computed tomography images, acquired after verification beams, showed that the offset between the radiation isocenter and the imaging center was within 0.66 mm for 90 months. The isocenter localization accuracy within 1 mm was kept for long period at other four institutions. CONCLUSIONS: Long-term analysis showed the feasibility of VS analysis for isocenter localization QA, including room laser re-alignment, noncoplanar irradiation verification, and image guidance accuracy.

Prolonged Neoadjuvant Therapy for Locally Advanced Pancreatic Cancer.

PURPOSE: The purpose of this study was to investigate if prolonged neoadjuvant therapy, for locally advanced pancreatic cancer could be used to identify those patients who could benefit from resection surgery. METHODS: Thirty-four patients with locally advanced pancreatic cancer invading the adjacent major arteries underwent chemoradiotherapy, followed by 6 months of systemic chemotherapy, unless their tumor was already resectable. After this combination treatment, surgical resection was performed on those patients with tumors judged to be at least borderline resectable. RESULTS: Reevaluation after chemoradiotherapy revealed that, at that stage, surgery was only possible for one case; resection was successfully performed. Following 6 months of systemic chemotherapy, a further 7 patients were diagnosed with borderline resectable lesions; 4 underwent surgery with no postoperative complications. The median survival time of the patients following surgery was 3.63 years; this was reduced to approximately a third in patients not undergoing surgery (1.01 years; p = 0.0005). CONCLUSIONS: For patients with locally advanced pancreatic cancer, prolonged neoadjuvant therapy was successfully used to select candidates that could benefit from surgical resection of their tumor. Resection significantly increased the long-term survival rate.

Radiotherapy for vaginal cancer: a multi-institutional survey study of the Japanese Radiation Oncology Study Group.

PURPOSE: Our aim was to assess the patterns of practice and treatment outcomes of definitive radiotherapy (RT) for vaginal cancer in Japan. MATERIALS AND METHODS: RT methods and outcomes of patients with vaginal cancer treated with definitive RT or chemoradiotherapy at 10 institutes of the Japanese Radiation Oncology Study Group between January 2000 and March 2010 were retrospectively evaluated. RESULTS: A total of 90 patients were enrolled in the study. The clinical stages were I, II, III, and IVA in 34, 36, 16, and 4 patients, respectively. Seventy patients were treated with three-dimensional conformal RT (3DCRT) and brachytherapy (BT), 12 with BT alone, and 8 with 3DCRT alone. Chemotherapy was administered to 29 patients. The 5-year overall survival and local control rates were 77 and 83% with a median follow-up period of 94 months for surviving or lost patients. The 5-year overall survival rates according to stage were 94, 71, 56, and 75% for stages I, II, III, and IVA, respectively. The 5-year local control rates according to stage were 94, 77, 74, and 75% for stages I, II, III, and IVA, respectively. Twenty-nine percent (6 of 21 patients) of local recurrences occurred between 5 and 10 years after RT. The 10-year local control rate of all patients was 71%. Significant prognostic factors for overall survival by univariate and multi-variate analyses were performance status, tumor size, and pelvic lymph node metastasis. Grade 3 late radiation morbidity of the rectum, pelvic bone, urinary bladder, and skin developed in 9% (8 of 90 patients). CONCLUSIONS: Good outcomes similar to those of cervical cancer can be achieved with definitive RT delivered by 3DCRT and/or BT for vaginal cancer. Long follow-up is necessary for a continuing risk of local recurrence after 5 years.

Metabolic tumor volume of primary tumor predicts survival better than T classification in the larynx preservation approach.

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T-MTV) or T classification would be a better predictor of laryngectomy-free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T-MTV cut-off value was determined by time-dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T-MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T-MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T-MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97-8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47-6.69; P = 0.004) compared with small T-MTV (≤28.7 mL). The T-MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three-year LFS and OS rates for patients with small versus large T-MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2-T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99-1.00). Given the excellent interobserver reliability, T-MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.

Predictors of distant relapse in patients with FIGO stage IIB-IVA cervical cancer treated with definitive radiotherapy.

AIM: To investigate the predictors of distant relapse in International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer patients treated with definitive radiotherapy (RT). METHODS: The clinical data of 219 patients with FIGO stage IIB-IVA cervical cancer treated with definitive RT between January 1997 and December 2011 were retrospectively reviewed. The cumulative distant relapse, progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was used to investigate the predictors of distant relapse in patients. RESULTS: Following treatment with definitive RT, 61 of the 219 (27.9%) patients developed distant relapse with median PFS and OS rates of 9.9 and 32.8 months, and estimated five-year PFS and OS rates of 4.9% and 21.3%, respectively. Multivariate analysis revealed that pelvic node metastasis, pretreatment leukocytosis and pretreatment neutrophilia were significant predictors of distant relapse. The risk of developing distant relapse was found to be associated with the number of predictors that the patients displayed: the estimated five-year distant relapse rates of the patients with no predictors, one predictor and two predictors were 20.3%, 35.5% and 88.9%, respectively. CONCLUSIONS: Roughly 28% of patients with FIGO stage IIB-IVA cervical cancer developed distant relapse after definitive RT. Pelvic lymph node metastasis and pretreatment leukocytosis/neutrophilia are independent predictors of distant relapse.

A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes.

OBJECTIVES: A phase II study was conducted to evaluate the efficacy and toxicity of carboplatin plus paclitaxel (TC)-based postoperative concurrent chemoradiotherapy (CCRT) followed by TC-based consolidation chemotherapy in surgically-treated early-stage cervical cancer patients. METHODS: Women with surgically-treated early-stage cervical cancer with positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic intensity modulated radiotherapy (50.4Gy) and concurrent weekly carboplatin (AUC: 2) and paclitaxel (35mg/m(2)) (TC-based CCRT). Three cycles of consolidation chemotherapy involving carboplatin (AUC: 5) and paclitaxel (175mg/m(2)) were administered after TC-based CCRT. RESULTS: Thirty-one patients were enrolled and treated. Overall, the treatment was well tolerated, and 26 patients (83.9%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up period of 36.5months, 2 patients (6.5%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 93.8%, respectively. In comparisons with historical control groups, TC-based CCRT followed by TC-based consolidation chemotherapy was found to be significantly superior to CCRT involving a single platinum agent in terms of PFS (p=0.026) and significantly superior to extended-field radiotherapy in terms of both PFS (p=0.0004) and OS (p=0.034). CONCLUSIONS: In women with surgically treated early-stage cervical cancer, pelvic TC-based CCRT followed by TC-based consolidation chemotherapy is feasible and highly effective. Future randomized trials are needed to verify the efficacy of this regimen.

Chemoradiotherapy with weekly low-dose docetaxel and cisplatin concurrent with radiation for patients with locally advanced nasopharyngeal carcinoma, followed by adjuvant chemotherapy for selected patients.

OBJECTIVE: We investigated the efficacy and safety of concurrent chemoradiotherapy using weekly low-dose docetaxel and cisplatin in patients with locally advanced nasopharyngeal carcinoma. METHODS: This was a retrospective analysis of 31 patients who were treated with this regimen from 2001 to 2014. Concurrent chemoradiotherapy consisted of radiotherapy with a total dose of 59.4-70.2 Gy plus weekly administration of docetaxel (5-10 mg/m2) and cisplatin (20 mg/m2), up to six cycles. At least two cycles of platinum-based adjuvant chemotherapy were prescribed for Stage IV and Stage III patients with partial response or stable disease after concurrent chemoradiotherapy. RESULTS: Of the 31 patients, 28 (90%) completed concurrent chemoradiotherapy as planned. The overall complete response and partial response rates were 42% and 52%, respectively. Seventeen of the 21 patients who were prescribed adjuvant chemotherapy underwent it. After a median follow-up of 39.1 months for the 23 surviving patients, 9 (29%) developed locoregional recurrence or progression and 6 patients (19%) developed distant metastasis. The 3-year overall survival and progression-free survival rates were 76% and 56%, respectively. Univariate analyses revealed that clinical stage was a significant predictor of complete response, overall survival and progression-free survival. The most serious adverse events were mucositis during concurrent chemoradiotherapy and neutropenia during adjuvant chemotherapy. CONCLUSIONS: This concurrent chemoradiotherapy protocol showed practical efficacy with high feasibility and acceptable toxicity. To improve the progression-free survival of patients with Stage IV disease who are treated by this protocol, changes to their treatment strategy should be considered.

Predictors of Survival in Patients With FIGO Stage IVB Cervical Cancer.

OBJECTIVE: The aim of this study was to identify prognostic factors and establish a model for predicting life expectancy in International Federation of Gynecology and Obstetrics stage IVB cervical cancer patients. METHODS: The baseline characteristics and outcome data of patients with stage IVB cervical cancer between May 1994 and October 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to identify independent predictors of survival in stage IVB cervical cancer patients. RESULTS: A total of 107 patients were included in our database. The median overall survival (OS) period was 16 months. Multivariate analysis revealed that the metastatic site (hazards ratio, 3.09; 95% confidence interval, 1.94-4.88; P < 0.0001) and a white blood cell (WBC) count exceeding 10,000/µL (hazards ratio, 2.02; 95% confidence interval, 1.19-3.30; P = 0.0102) were significant prognostic factors in terms of OS. Patient survival was inversely correlated with the number of these prognostic factors possessed. When the patients were divided into 3 prognostic groups, the median OS of the patients with 0, 1, or 2 poor prognostic factors was 26, 12, and 7 months, respectively. Among the patients with WBC counts of less than 10,000/µL, treatment with radiotherapy resulted in improved survival compared with chemotherapy or palliative care alone. In contrast, radiotherapy had minimal effects on survival in patients with WBC counts of greater than 10,000/µL. CONCLUSIONS: The metastatic site and an elevated WBC count are significant prognostic factors in patients with stage IVB cervical cancer. Our prognostic model composed of these 2 clinical variables might enable physicians to predict survival more accurately.