Anhui Shi

Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy

BackgroundTo evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT).MethodsWe analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP.ResultsMedian follow-up was 10.5 months (range 6.5-24). Of 94 patients, 11 (11.7%) developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP), mean lung dose (MLD), relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60), chronic obstructive pulmonary disease (COPD) and Forced Expiratory Volume in the first second (FEV1) were associated with SARP (p < 0.05). In multivariate analysis, NTCP value (p = 0.001) and V10 (p = 0.015) were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP ≤4.2% were 43.5% and 1.4%, respectively (p < 0.01). The incidences of SARP in the group with V10 ≤50% and V10 >50% were 5.7% and 29.2%, respectively (p < 0.01).ConclusionsNTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.

Volumetric-modulated arc therapy vs c-IMRT in esophageal cancer: A treatment planning comparison

AIM To compare the volumetric-modulated arc therapy (VMAT) plans with conventional sliding window intensity-modulated radiotherapy (c-IMRT) plans in esophageal cancer (EC). METHODS Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning system: three using c-IMRT with 5 fields (5F), 7 fields (7F) and 9 fields (9F), and two using VMAT with a single arc (1A) and double arcs (2A). The treatment plans were designed to deliver a dose of 60 Gy to the planning target volume (PTV) with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normalized to 95% of the PTV that received 100% of the prescribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk (OAR) such as lungs, spinal cord and heart. Monitor units (MU) and normal tissue complication probability (NTCP) of OAR were also reported. RESULTS Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different locations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions: in cervical and upper thoracic EC, the conformity index (CI) was higher in VMAT (1A 0.78 and 2A 0.8) than in c-IMRT (5F 0.62, 7F 0.66 and 9F 0.73) and homogeneity was slightly better in c-IMRT (7F 1.09 and 9F 1.07) than in VMAT (1A 1.1 and 2A 1.09). Lung V30 was lower in VMAT (1A 12.52 and 2A 12.29) than in c-IMRT (7F 14.35 and 9F 14.81). The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT (1A 0.76 and 2A 0.74) was higher than in c-IMRT (5F 0.63 Gy and 7F 0.67 Gy), and homogeneity was almost similar between VMAT and c-IMRT. V20 (2A 21.49 Gy vs. 7F 24.59 Gy and 9F 24.16 Gy) and V30 (2A 9.73 Gy vs. 5F 12.61 Gy, 7F 11.5 Gy and 9F 11.37 Gy) of lungs in VMAT were lower than in c-IMRT, but low doses to lungs (V5 and V10) were increased. V30 (1A 48.12 Gy vs. 5F 59.2 Gy, 7F 58.59 Gy and 9F 57.2 Gy), V40 and V50 of heart in VMAT was lower than in c-IMRT. MUs in VMAT plans were significantly reduced in comparison with c-IMRT, maximum doses to the spinal cord and mean doses of lungs were similar between the two techniques. NTCP of spinal cord was 0 for all cases. NTCP of lungs and heart in VMAT were lower than in c-IMRT. The advantage of VMAT plan was enhanced by doubling the arc. CONCLUSION Compared with c-IMRT, VMAT, especially the 2A, slightly improves the OAR dose sparing, such as lungs and heart, and reduces NTCP and MU with a better PTV coverage.

Feasibility of omitting clinical target volume for limited-disease small cell lung cancer treated with chemotherapy and intensity-modulated radiotherapy

PurposeTo analyze the feasibility of omitting clinical target volume (CTV) for limited small cell lung cancer treated with chemotherapy and intensity modulated radiotherapy.Methods and materials89 patients were treated from January 1, 2008 to August 31, 2011, 54 cases were irradiated with target volume without CTV, and 35 cases were irradiated with CTV. Both arms were irradiated post chemotherapy tumor extent and omitted elective nodal irradiation; dose prescription was 95% PTV56-63 Gy/28-35 F/5.6-7 weeks.ResultsIn the arm without CTV and arm with CTV, the local relapse rates were 16.7% and 17.1% (p = 0.586) respectively. In the arm without CTV, of the 9 patients with local relapse, 6 recurred in-field, 2 recurred in margin, 1 recurred out of field. In the arm with CTV, of the 6 patients with local relapse, 4 recurred in-field, 1 recurred in margin, 1 recurred out of field. The distant metastases rates were 42.6% and 51.4% (p = 0.274) respectively. Grade 3-4 hematological toxicity and radiation esophagitis had no statistically significant, but grade 3-4 radiation pneumonia was observed in only 7.4% in the arm without CTV, compared 22.9% in the arm with CTV (p = 0.040). The median survival in the arm without CTV had not reached, compared with 38 months in the with CTV arm. The l- years, 2- years, 3- years survival rates of the arm without CTV and the arm with CTV were 81.0%, 66.2%, 61.5% and 88.6%, 61.7%, 56.6% (p = 0.517). The multivariate analysis indicated that the distant metastases (p = 0.000) and PCI factor (p = 0.004) were significantly related to overall survival.ConclusionsTarget delineation omitting CTV for limited-disease small cell lung cancer received IMRT was feasible. The distant metastases and PCI factor were significantly related to overall survival.

Phase I study to determine MTD of docetaxel and cisplatin with concurrent radiation therapy for stage III non-small cell lung cancer

ObjectiveTo evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer (stage IIIa and IIIb) after 2–4 cycles of induction chemotherapy.MethodsFourteen patients with histological/cytological proven stage III non-small-cell lung cancer were eligible. 3D or IMRT radiotherapy (60–70Gy in 30–35 fractions, 6–7weeks, 2 Gy/fraction) was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy (CCRT). The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/m2 DDP, on day 1 and day 2.ResultsFourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III (64 mg/m2) and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients.ConclusionsPatients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2–3 cycles of induction chemotherapy.

Phase I study to determine the MTD of paclitaxel given three times per week during concurrent radiation therapy for stage III non-small cell lung cancer

ABSTRACT Objective: To evaluate the toxicity and the maximum tolerated dose (MTD) of paclitaxel concurrently with three-dimensional (3D) conformal radiotherapy for patients with locally advanced non-small cell lung cancer (LANSCLC) after 2–3 cycles of induction chemotherapy. Research design and methods: Patients with histologically proven stage III non-small cell lung cancer (NSCLC) were eligible. Induction chemotherapy regimen included cisplatin (40 mg/m2) on days 1 and 2, and vinorelbine (25 mg/m2) on days 1 and 8 every 3 weeks for 2 or 3 cycles, followed a month later by continual three-dimensional (3D) conformal radiotherapy (60 Gy in 30 fractions for 6 weeks) delivered concurrently with paclitaxel dose escalating from the lowest level, 15 mg/m2, twice weekly, 6 weeks in all, to the highest level, 15 mg/m2, three times a week, 6 weeks in all. Main outcome measures: The MTD was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity, with the next higher dose having at least two out of six patients experience dose-limiting toxicity (DLT). Results: Twenty-three patients were enrolled in this study. The maximum tolerated dose of paclitaxel during 3D-conformal radiotherapy was not reached at 15 mg/m2, three times a week, 6 weeks in all, a level which has been recommended for Caucasian patients with LANSCLC without induction chemotherapy. The overall response rate of induction chemotherapy alone was 47.8% (0% complete remission, 47.8% partial remission, 39.1% stable disease, 13% progressive disease) and that of induction chemotherapy plus concurrent treatment was 78.3% (18/23), including 8.7% (2/23) complete remissions. None of the patients died as a result of toxicity. The median survival time was 23.0 months. Conclusions: 15 mg/m2 of paclitaxel, three times a week, concurrently with 3D-conformal radiotherapy for patients with locally advanced NSCLC after 2 or 3 cycles of induction chemotherapy is a safe and effective dose, according to our preliminary study.

Deficiencies in the Diagnosis and Treatment of Pulmonary Metastatic Osteosarcoma: A Chinese Multidisciplinary Survey

BACKGROUND AND OBJECTIVE Osteosarcoma is the most frequent primary cancer of bone. The incidence is higher in adolescents. Large improvement, though, has been made in the treatment of osteosarcoma under the framework of multidisciplinary team, an important prognostic factor for osteosarcoma is pulmonary metastasis. Surgical resection of lung metastases is widely accepted as the optimal modality in osteosarcoma patients. Undoubtedly, surgical resection of lung metastases is widely accepted as the optimal modality in osteosarcoma patients. However, since current conceptions within the surgical approach to lung metastasectomy involve multidisciplinary collaboration, which are highly variable,there is not neither consensus nor standardized practice patterns. We conduct a survey aiming to reveal areas of consistency in current clinical practice on lung metastasectomy among Chinese osteosarcoma high volume centers. METHODS A questionnaire survey specific to the nationwide high volume centers of osteosarcoma was conducted from September 2015 to November 2015. Analyses were stratified by hospital, working duration, case volume and medical discipline. RESULTS Of 150 invited physicians, 105 participated, resulting in an overall response rate of 70%. Forty-one percent of the responded physicians agreed with the statement that orthopedic oncology should play a predominant role in the multidisciplinary team. More than 64% of respondents chose metastasectomy as the preferred local control approach, and up to 78.1% of respondents recommended pulmonary metastasectomy for patients. Compared with orthopedic surgeons, other physicians were significantly more likely to report not advocating pulmonary metastasectomy in their practice (OR(others)=0.02; 95%CI: 0.00-0.22; P=0.001), and thoracic surgeons were more likely to decide metastasectomy according to indications rather than the number limit of metastases (OR(thoracic surgeons)=20.93; 95%CI: 2.05-213.64; P=0.001). For the most preferred radiographic evaluation option, approximately 83% of respondents reported diagnostic use of computed tomography (CT). More than 70% of respondents reported that chest CT follow-up should be 3 months after the primary site resection; approximately 68% deemed the diagnostic accuracy of CT about 90%; most respondents (92%) recommended the extrapulmonary imaging evaluation simultaneously. Around 46% of respondents reported that survival duration longer than 6 months after pulmonary metastasectomy is beneficial. CONCLUSION This study offers new information about the variability in the reported management of pulmonary metastatic osteosarcoma in China, reflecting the deficiencies in unified practice patterns. The results of this survey also provide baseline data for future research and for the development of international guidelines.

Posttreatment Immune Parameters Predict Cancer Control and Pneumonitis in Stage I Non–Small-Cell Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy

&NA; Stereotactic ablative body radiotherapy can increase the total number of cytotoxic CD8+ T lymphocytes and regulatory T cells among peripheral lymphocytes. Increased cytotoxic CD8+ T‐cell level was an independent prognostic factor for longer progression‐free survival in stage I non–small‐cell lung cancer. Proportion of lung receiving 20 Gy of radiotherapy and mean lung dose are independent predictors of symptomatic radiation pneumonitis (grade 2 or higher); neither pretreatment nor posttreatment T lymphocyte subset level was significantly related to symptomatic radiation pneumonitis (grade 2 or higher). Purpose: Stereotactic ablative body radiotherapy (SABR) represents an exciting, tolerable, and highly effective form of radiotherapy. Ongoing investigations into the interactions between radiotherapy and the immune system have uncovered new mechanisms that can be exploited to improve efficacy. We determined whether baseline or posttreatment immune parameters could predict disease control and toxicity in stage I non–small‐cell lung cancer (NSCLC) patients treated with SABR. Patients and Methods: Peripheral blood samples were collected from 62 patients 24 hours before treatment and within 4 weeks after treatment for lymphocyte subset count analysis. All peripheral blood samples were analyzed by flow cytometry. Associated parameters were evaluated to determine their association with progression‐free survival (PFS) and symptomatic radiation pneumonitis (grade 2 or higher). The survival rates were estimated with Kaplan‐Meier and multivariable analyses using binary logistic regression analysis or a Cox proportional hazards model. Results: At a median follow‐up time of 36.0 months, the PFS rates for years 1, 2, and 3 were 91.0%, 82.5%, and 48.9%, respectively. The multivariable logistic regression analysis showed that only proportion of lung receiving 20 Gy of radiotherapy (odds ratio = 1.41; 95% confidence interval, 1.05‐1.87; P = .023) and mean lung dose (odds ratio = 2.02; 95% confidence interval, 1.16‐3.53; P = .016) were associated with symptomatic radiation pneumonitis (grade 2 or higher). Moreover, the immune parameters had no predictive value. In the multivariable Cox regression analysis, an elevated posttreatment cytotoxic CD8+ T‐cell level was an independent prognostic factor for longer PFS in stage I NSCLC (hazard ratio, 1.16; 95% confidence interval, 1.01‐1.28; P = .01). Conclusion: A higher posttreatment cytotoxic CD8+ T‐cell level was predictive of better PFS in stage I NSCLC patients receiving SABR. Thus, enhancing tumor antigen‐specific cellular immunity by combining radiotherapy and immunotherapy might be a crucial strategy for improving survival in these patients.

[Phase I Study of Etoposide and Cisplatin Chemotherapy Dose Escalation â©with Concurrent Twice-daily Radiotherapy for Patients â©with Limited-stage Small Cell Lung Cancer].

BACKGROUND Concurrent twice-daily radiotherapy with chemotherapy of EP regimen is one of the current standard treatments for limited-stage small cell lung cancer. However, the safely tolerated dose of standard chemotherapy for Chinese patients is not decided. This study was to evaluate the toxicity and the maximum tolerated dose (MTD) of etoposide and cisplatin concurrent with thoracic radiation therapy for patients with limited-stage small cell lung cancer. METHODS Patients with histologically proven limited-stage small cell lung cancer (LS-SCLC) were eligible. The patients underwent thoracic radiotherapy (45 Gy, 1.5 Gy bid, 30 fractions for 3 weeks) delivered concurrently with etoposide (100 mg/m2 iv, days 1-3) and cisplatin dose escalating from the two levels ( 70 mg/m2 and 75 mg/m2 on d1). The primary endpoints were hematologic toxicities during treatment. The secondary endpoints were non-hematologic toxicities, overall survival (OS) and progression-free survival (PFS). According to Common Terminology Criteria for Adverse Events 4.0 (CTC-AE 4.0), maximum tolerant dosage (MTD) was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity (Grades 4 hematologic), with the next higher dose having at least two out of six patients experience dose-limiting toxicity. RESULTS From January 2013 to August 2016, 20 patients were enrolled in this study. The median age was 49.5 (30-68). After the first 6 patients were enrolled in Arm 1 (70 mg/m2 on d1), one patient had Grade 4 neutropenia. Another 14 patients were enrolled in Arm 2 (75 mg/m2 on d1), one patient had Grade 4 neutropenia. The MTD was determined to be etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1). 4 patients had ≥Grade 3 neutropenia and 1 patients had ≥Grade 3 acute esophagitis in Arm 1. 10 patients had ≥Grade 3 neutropenia and no patient had ≥Grade 3 acute esophagitis in Arm 2. All patients with a median follow-up time was 9.0 months, median OS and PFS were not achieved, 1-year OS and PFS were 91% and 61%, respectively. CONCLUSIONS The MTD of RT with concurrent chemotherapy of EP regimen for patients with LS-SCLC was etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1).
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Phase 3 Randomized Low-Dose Paclitaxel Chemoradiotherapy Study for Locally Advanced Non-Small Cell Lung Cancer

Introduction Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with poor chest tumor control. Here, we report results of a randomized phase 3 study comparing two CCRT regimens in improving chest tumor control by low-dose paclitaxel chemoradiation for LA-NSCLC. Methods Due to the logistics of local referral pattern, the study was designed to enroll patients with stage III LA-NSCLC who had completed 2–4 cycles of full-dose chemotherapy. One hundred thirty four were randomized to either Arm 1 [paclitaxel at 15 mg/m2, three times per week (Monday, Wednesday, and Friday) for 6 weeks, n = 74] or Arm 2 (weekly paclitaxel at 45 mg/m2 for 6 weeks, n = 60). Chest radiotherapy was 60–70 Gy in standard fractionation. Response rate was the primary endpoint, with recurrence-free survival (RFS) as the secondary endpoint. Results From March 2006 to February 2013, 71 patients completed Arm 1 treatment and 59 completed Arm 2 treatment. The response rate for Arm 1 was significantly higher (83.1%) than Arm 2 (54.2%) (p=0.001). RFS was superior in Arm 1: median 14.6 vs. 9.4 months, p = 0.005, Hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.20, 2.90]. Overall survival was not significantly different: median 32.6 months in Arm 1 vs. 31.3 months in Arm 2, p = 0.91, HR 0.97 (95% CI 0.55, 1.70). Toxicity was significantly lower in Arm 1 for Grade 3 and 4 leukopenia/neutropenia (p < 0.001). Conclusion Pulsed low-dose paclitaxel CCRT resulted in significantly better RFS and tumor response rate, and less hematologic toxicities than weekly CCRT for LA-NSCLC.