3D-CRT Group Research Articles

Effectiveness and acute toxicity of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in pancreatic cancer: a systematic review and a meta-analysis

Background: Intensity-modulated radiotherapy (IMRT) produces a concave dose distribution to reduce gastrointestinal (GI) toxicity in patients with pancreatic cancer. The aim of this study is to summarize the current evidence on the survival and organ toxicity of IMRT in comparison with three-dimensional conformal radiotherapy (3D-CRT). Method: A search was conducted in the PubMed and EMBASE databases to identify studies that reported survival and radiation toxicity of IMRT compared to 3D-CRT. The primary endpoint for comparison was 1-year overall survival (OS). Pooled effect estimates were calculated using fixed-effect or random-effect models for all-cause mortality, acute GI toxicity and hematologic (HEMA) toxicity. Results: The initial search yielded a total of 528 articles from PubMed and EMBASE. After inclusion and exclusion based on pre-defined criteria, eight studies with head-to-head comparisons between IMRT and 3D-CRT were included for final analysis. In meta-analysis, The IMRT group was associated with a reduced 1-year mortality [relative risk (RR) =0.92; 95% confidence interval (CI): 0.86–0.99, P=0.017] and 2-year mortality (RR =0.96; 95% CI: 0.94–0.99, P=0.001). The radiation-induced ≥ grade 3 GI toxicity rate was significantly lower in the IMRT group than in the 3D-CRT group (RR =0.69; 95% CI: 0.50–0.96, P=0.046), while the HEMA toxicity was comparable between IMRT and 3D-CRT groups (RR: 1.13, 95% CI: 0.89–1.44, P=0.716). Conclusions: Despite several methodological and sample size limitations, reports from the current literature suggest a moderate survival advantage and attenuated GI toxicity of IMRT as compared with 3D-CRT. HEMA toxicity were found no significant difference between IMRT and 3D-CRT.

Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis and systematic review

PurposeWe performed a meta-analysis and systematic review to compare the radiotherapy (RT) modalities for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Materials and methodsWe searched the PubMed, EMBASE, Medline, and Cochrane library databases. The primary endpoint was the 1-year overall survival (OS), and response rate (RR), local control (LC), 2-year OS, and grade ≥3 toxicity incidence were evaluated as secondary endpoints. ResultsThirty-seven studies comprising 2513 patients were included. The pooled 1-year OS rates for the 3-dimensional conformal RT (3DCRT), selective internal RT (SIRT), and stereotactic body RT (SBRT) groups were 43.8% [95% confidence interval (CI): 37.6–50.2], 46.5% (95% CI: 37.7–55.6), and 48.5% (95% CI: 39.4–57.8). These inter-group differences were not statistically significant (p = 0.635). The pooled response rates were 51.3% (95% CI: 45.7–57.0), 33.3% (95% CI: 18.0–53.2), and 70.7 (95% CI: 63.7–76.8) for 3DCRT, SIRT, and SBRT groups, respectively; p = 0.001 and 0.031 for 3DCRT vs. SBRT and SIRT, respectively. The most common grade ≥ 3 complications were lymphocytopenia and bilirubin abnormalities in the 3DCRT and SIRT groups, respectively. Grade ≥ 3 complication was rare in SBRT group. ConclusionsOS did not differ among the modalities, although the response rates vary among modalities.

Impact of Intensity-Modulated Radiotherapy on Health Care Costs of Patients With Anal Squamous Cell Carcinoma.

Drivers of variation in the cost of care after chemoradiotherapy for the management of anal squamous cell carcinoma (SCC) have not been fully elucidated. We sought to characterize the direct and indirect impact of radiotherapy modality on health care costs among patients with anal SCC. A retrospective cohort study was performed using the 2014 linkage of the SEER-Medicare database. We identified 1,025 patients with anal SCC diagnosed between 2001 and 2011 and treated with chemoradiotherapy. Propensity score matching was used to balance baseline differences between patients treated with intensity-modulated radiotherapy (IMRT) and those treated with three-dimensional conformal radiotherapy (3D-CRT). Differences in total, cancer-attributable, and procedure-specific costs between groups were measured. Radiation-related, patient out-of-pocket, and total costs in the 1-year period after radiotherapy start were all higher for the IMRT group than the 3D-CRT group (median total cost, $35,890 v $27,262, respectively; P < .001). Patients who received IMRT had lower cumulative costs associated with urgent hospitalizations and emergency department visits at both 9 months and 1 year after treatment start compared with a matched cohort of patients who received 3D-CRT (median, $711 v $4,957 at 1 year, respectively; P = .021). Although total costs of care were higher for IMRT compared with 3D-CRT, primarily as a result of higher radiotherapy-specific costs, IMRT was associated with decreased unplanned health care utilization costs starting at 9 months after treatment start. Radiotherapy-centered episodes of care may need to encompass a longer time horizon to capture the full cost savings associated with more advanced radiation modalities.

Quality of Life in Patients Who Underwent Intensity-Modulated Radiation Therapy, 125 I Brachytherapy, and Combined 125 I Brachytherapy Plus Three-Dimensional Conformal Radiation Therapy for Prostate Cancer

To evaluate quality of life (QOL) in patients who underwent intensity-modulated radiation therapy (IMRT), I125 brachytherapy (BT), and BT combined with three-dimensional conformal radiation therapy (BT + 3D-CRT) for prostate cancer (PCa) patients. We conducted a prospective trial to evaluate health-related QOL for patients who underwent IMRT, BT, and BT + 3D-CRT. QOL was estimated by the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before each treatment and at 1, 3, 6, 12, and 24 months. Multivariate analyses were conducted to determine factors associated with lowering urinary and bowel domain scores at 12 months from baseline. Data were analyzed from 555 (IMRT: n = 123, BT: n = 227, BT + 3D-CRT: n = 205) at 12 months. Mean change in the urinary summary score at 12 months was −0.01, −3.4, and −4.1 points among patients treated with IMRT, BT, and BT + 3D-CRT, respectively. Mean change in the bowel summary score at 12 months was −3.5, −1.1, and −2.8 points among patients treated with IMRT, BT, and BT + 3D-CRT, respectively.On multivariate analysis of factors that predict a lower EPIC score of the urinary domain at 12 months, BT (OR 1.91, 95% CI 1.11–3.28) and BT + 3D-CRT (OR 2.14, 95% CI 1.24–3.70) groups had lower urinary QOL at 12 months using the IMRT group as a reference. In addition, on multivariate analysis of factors that predict a lower EPIC score of the urinary domain at 24 months, BT (OR 1.82, 95% CI 1.04–3.20) and BT + 3D-CRT (OR 3.11, 95% CI 1.77–5.48) groups had lower urinary QOL using the IMRT group as a reference.On multivariate analysis of factors predicting a lower EPIC score in the bowel domain, the BT + 3D-CRT (OR 1.59, 95% CI 1.06–2.37) and IMRT (OR 2.22, 95% CI 1.33–3.74) groups had lower bowel QOL using the BT group as a reference at 12 months. In addition, on multivariate analysis of factors that predict a lower EPIC score of the bowel domain at 24 months, the BT + 3D-CRT (OR 1.59, 95% CI 1.02–2.49) and IMRT (OR 1.68, 95% CI 1.002–2.82) groups had lower bowel QOL using the BT group as a reference. Knowledge of changes in QOL outcomes associated with IMRT, BT, and BT + 3D-CRT may influence treatment recommendations and enable patients to make better-informed decisions.

Simultaneous integrated boost intensity-modulated radiotherapy versus 3-dimensional conformal radiotherapy in preoperative concurrent chemoradiotherapy for locally advanced rectal cancer.

PurposeTo evaluate the feasibility of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for preoperative concurrent chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC), by comparing with 3-dimensional conformal radiotherapy (3D-CRT).Materials and MethodsPatients who were treated with PCRT for LARC from 2015 January to 2016 December were retrospectively enrolled. Total doses of 45 Gy to 50.4 Gy with 3D-CRT or SIB-IMRT were administered concomitantly with 5-fluorouracil plus leucovorin or capecitabine. Surgery was performed 8 weeks after PCRT. Between PCRT and surgery, one cycle of additional chemotherapy was administered. Pathologic tumor responses were compared between SIB-IMRT and 3D-CRT groups. Acute gastrointestinal, genitourinary, hematologic, and skin toxicities were compared between the two groups based on the RTOG toxicity criteria.ResultsSIB-IMRT was used in 53 patients, and 3D-CRT in 41 patients. After PCRT, no significant differences were noted in tumor responses, pathologic complete response (9% vs. 7%; p = 1.000), pathologic tumor regression Grade 3 or higher (85% vs. 71%; p = 0.096), and R0 resection (87% vs. 85%; p = 0.843). Grade 2 genitourinary toxicities were significantly lesser in the SIB-IMRT group (8% vs. 24%; p = 0.023), but gastrointestinal toxicities were not different across the two groups.ConclusionSIB-IMRT showed lower GU toxicity and similar tumor responses when compared with 3D-CRT in PCRT for LARC.

Efficacy of three-dimensional conformal radiotherapy in treatment of prostate cancer: a meta-analysis

Objective To systematically compare the efficacy of three-dimensional conformal radiotherapy (3D-CRT) versus intensity-modulated radiotherapy (IMRT) in the treatment of prostate cancer (PCa). Methods Clinical comparative studies of IMRT and 3D-CRT in the treatment of PCa were collected from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang Data after two independent researchers developed the strategy and inclusion and exclusion criteria for the literature search. Articles published up to February 2017 were searched for, and the languages of publications were restricted to English and Chinese. Clinical meta-analysis of the data from the relevant studies was performed using the RevMan5.3 software. Results A total of 15 relevant retrospective cohort studies were collected from the databases in strict accordance to the search strategy and inclusion and excluding criteria. There were 4608 PCa patients, including 2229 in the IMRT group and 2379 in the 3D-CRT group. IMRT and 3D-CRT had similar adverse effects in terms of early-stage (odds ratio[OR]=0.77, 95% confidence interval[CI]: 0.43-1.40, P=0.390) and late-stage (OR=0.75, 95%CI: 0.55-1.04, P=0.080) urinary tract injury. However, IMRT led to reduced early-stage (OR=0.47, 95%CI: 0.27-0.82, P=0.008) and late-stage (OR=0.52, 95%CI: 0.35-0.78, P=0.001) intestinal injury compared with 3D-CRT. Meanwhile, the biochemical recurrence-free survival rate was also significantly higher in the IMRT group than in the 3D-CRT group (OR=1.87, 95%CI: 1.51-2.32, P=0.000). Conclusions IMRT is more protective against intestinal injury with a higher biochemical recurrence-free survival rate compared with 3D-CRT during the treatment of PCa. Key words: Prostate neoplasms/intensity-modulated radiotherapy; Prostate neoplasms/three-dimensional conformal radiotherapy; Meta-analysis

Moderate dose escalation with volumetric modulated arc therapy improves outcome in rectal cancer

Background: Locally advanced rectal cancer is frequently treated with a long course of preoperative chemoradiotherapy. We investigated the effect of moderate dose escalation with volumetric modulated arc therapy (VMAT) up to 50 Gy in 25 fractions compared to 3D conformal radiotherapy (3D-CRT) to 45 Gy in 25 fractions in rectal cancer patients. Dose–volume parameters, acute toxicity, and complete response rates were compared.Material and Methods: For both groups, 65 patients were selected from our database through availability. Dose–volume parameters and acute toxicity data were compared using a Mann–Whitney U-test. Univariate and multivariate analyses correcting for tumor and nodal stage, distance to the mesorectal fascia and interval to surgery were used to compare complete response rates.Results: Lower mean doses to the small and large bowel were observed in the VMAT group compared to the 3D-CRT group (21 Gy vs. 29 Gy [p < .001] and 26 Gy vs. 30 Gy [p = .002], respectively). Similar beneficial dose–volume parameters were observed for the bladder, sacrum and femoral heads. Furthermore, patients receiving VMAT experienced significantly less diarrhea, flatulence, non-infective cystitis, urinary frequency, dermatitis, and fatigue. In univariate analysis, a significant increase in complete response rate after moderate dose escalation with VMAT was observed (34% vs. 15%, p = .015). However, this did not remain significant when corrected for tumor and nodal stage, distance to the mesorectal fascia, and interval to surgery.Conclusions: Moderate dose escalation with VMAT resulted in superior dose–volume parameters compared to 3D-CRT, translating into lower acute toxicity. Additionally, improved tumor response after VMAT up to 50 Gy might contribute to a higher percentage of patients achieving a complete response.

Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity

BackgroundThough the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts.MethodsWe retrospectively analyzed 93 patients (3DCRT n = 49, IMRT n = 44) who received dCRT at our institution between 2000 and 2012 with the histologic diagnosis of nonmetastatic EC, a Karnofsky performance status of ≥70, curative treatment intent, and receipt of concomitant CRT. Patients were excluded if receiving <50 Gy. Kaplan-Meier analysis was used to evaluate the endpoints of local relapse rate (LR), progression-free survival (PFS), and overall survival (OS). Cox proportional hazards modeling addressed factors associated with outcomes with univariate and multivariate approaches. Rates of acute toxicities and basic dosimetric parameters were compared between 3DCRT and IMRT patients.ResultsMean follow-up was 34.7 months. The 3-year LR was 28.6% in the 3DCRT group and 22.7% in the IMRT group (p = 0.620). Median PFS were 13.8 and 16.6 months, respectively (p = 0.448). Median OS were 18.4 and 42.0 months, respectively (p = 0.198). On univariate analysis, only cumulative radiation dose was associated with superior LR (hazard ratio (HR) 0.736; 95% confidence interval (CI) 0.635 – 0.916, p = 0.004). Factors clearly affecting survival were not observed.ConclusionsWhen comparing 3DCRT- versus IMRT-based dCRT, no survival benefits were observed. However, we found a lower local recurrence rate in the IMRT group potentially owing to dose-escalation. Prospective data are needed to verify the presented results herein.

A randomized study of intensity-modulated radiation therapy versus three dimensional conformal radiation therapy for pelvic radiation in patients of post-operative treatment with gynecologic malignant tumor

Objective: To study the difference between intensity-modulated radiation therapy (IMRT) and three dimensional conformal radiation therapy (3D-CRT) for pelvic radiation of post-operative treatment with gynecologic malignant tumor. Methods: A prospective investigation study was conducted on 183 patients of post-operative patients with whole pelvic radiation therapy of cervical cancer or endometrial cancer in Zhejiang Cancer Hospital [IMRT group (n=85) and 3D-CRT group (n=98)] from Oct. 2015 to Oct. 2016. The two groups received same dose (45 Gy in 25 fractions). Comparison of two groups with radiation dosimetry:the score according to the Radiation Therapy Oncology Group (RTOG) acute radiation injury grading standards before and after radiotherapy reaction, the score from functional assessment of cancer therapy scale-cervix (FACT-Cx) scale and expanded prostate cancer index composite for clinical practice (EPIC-CP) scale were also analyzed. Results: (1) There were no significant effect with age, culture level, family economic condition and ratio of radiochemotherapy between two groups (all P>0.05). (2) Dosimetric comparison for IMRT vs 3D-CRT: the average dose of planning target volume (PTV) decreased (46.1±0.4) vs (46.4±0.5) Gy, V(45) dose percentage increased (95.2±1.0) % vs (93.3±2.0) %, intestinal bag dose of V(4)0 decreased (24.4±6.8) % vs (36.5±15.9) %, rectal V(40) dose percentage decreased (73.9±12.3) % vs (85.4±8.4) %, and lower rectal V(45) dose percentage (32.8±13.4) % vs (71.5±13.7) %, bladder V(40) dose percentage decreased (55.5±13.0) % vs (84.4±13.0) %. Bone marrow V(20) lower: (67.9±5.4) % vs (79.5±6.6) %, V(1)0 lower: (82.1±6.0) % vs (86.3±6.6) %; there were significant differences (all P<0.05). There was no significant difference between the dose of V(45) in the intestinal pouch and bladder (P>0.05). (3) Acute radiation injury classification for IMRT vs 3D-CRT: big or small intestine: Ⅱ-Ⅲ reaction [13% (11/85) vs 24% (24/98); χ(2)=3.925, P=0.048], there was significant difference. Bladder: Ⅲ reaction [19% (16/85) vs 26% (25/98); χ(2)=1.171, P=0.279], there was no significant difference. Radiochemotherapy of bone marrow suppression: Ⅲ-Ⅳ reaction (14/20), the incidence rate [26% (14/54) vs 31% (20/65); χ(2)=0.339, P=0.562], the difference was not statistically significant. (4) Quality of life scale by FACT-Cx scale in IMRT vs 3D-CRT: there were no significant difference before radiotherapy (82±16 vs 85±16; t=1.279, P=0.203), while there was significant difference after radiotherapy (76±14 vs 71±18; t=-2.160, P=0.032). EPIC-CP scale score: before radiotherapy they were (16±7 vs 15±6; t=-0.174, P=0.862),but after radiotherapy (18±7 vs 22±7; t=3.158, P=0.002), there was significant difference between them. Before and after radiotherapy, the increased EPIC-CP scale of the IMRT group vs 3D-CRT group were 3±4 and 6±4, the 3D-CRT group was significantly higher, the difference was statistically significant (t=5.500, P=0.000). Conclusion: IMRT has shown that there are a significant benefit for the post-operative patients with cervical cancer and endometrial cancer compared to 3D-CRT.

Intensity-modulated radiotherapy has superior outcomes to three-dimensional conformal radiotherapy in patients with stage IE-IIE extranodal nasal-type natural killer/T-cell lymphoma.

We compared the treatment outcomes, toxicities and prognoses of patients with stage IE-IIE extranodal natural killer/T-cell lymphoma (ENKTL) treated with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT). Newly diagnosed early-stage ENKTL patients (N = 173) were enrolled and received extended involved-field radiotherapy following induction chemotherapy. Patients were treated with 3DCRT (n = 98) or IMRT (n = 75). One-to-one matching of the IMRT and 3DCRT groups was performed through propensity score matching, which yielded 23 pairs of patients. The two groups achieved similar complete remission rates before and after radiotherapy (P > 0.05). All patients were followed up for a median of 41 months. The rates of local recurrence-free survival (LRFS, P < 0.001), progression-free survival (PFS, P = 0.003) and overall survival (OS, P = 0.003) were longer in the IMRT than 3DCRT group. In the matched patients, IMRT was still associated with superior LRFS (P = 0.024), but not with improved PFS (P = 0.113) or OS (P = 0.115). Multivariate analysis also suggested IMRT was a favorable independent factor for LRFS (HR = 2.230, P = 0.043), but not for PFS (P = 0.195) or OS (P = 0.116). Equivalent acute toxicities were observed for 3DCRT and IMRT; however, among stage II patients who had received cervical irradiation, the rate of late xerostomia was lower in the IMRT than 3DCRT group (38.5% vs. 66.7%, P = 0.046). Overall, IMRT yielded a better treatment response and local control than 3DCRT, and tended to reduce late xerostomia in patients with cervical irradiation, but failed to enhance OS. Thus, IMRT is recommended for the treatment of stage IE-IIE ENKTL patients.

Endovascular brachytherapy combined with portal vein stenting and transarterial chemoembolization improves overall survival of hepatocellular carcinoma patients with main portal vein tumor thrombus.

Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus have a median survival time of only about 4 months. We therefore compared the safety and efficacy of endovascular brachytherapy (EVBT) and sequential three-dimensional conformal radiotherapy (3-DCRT). From a cohort of 176 patients, we treated 123 with EVBT using iodine-125 seed strands (group A) and the remaining 53 with sequential 3-DCRT (group B). Overall survival, progression free survival and stent patency characteristics were compared between the two groups. Our analysis demonstrated a median survival of 11.7 ± 1.2 months in group A versus 9.5 ± 1.8 months in group B (p = 0.002). The median progression free survival was 5.3 ± 0.7 months in groupA versus 4.4 ± 0.4 months in group B (p = 0.010). The median stent patency period was 10.3 ± 1.1 months in group A versus 8.7 ± 0.7 months in group B (p = 0.003). Therefore, as compared to sequential 3-DCRT, EVBT combined with portal vein stenting and TACE improved overall survival of HCC patients with main portal vein tumor thrombus.

Comparison of survival rates between 3D conformal radiotherapy and intensity-modulated radiotherapy in patients with stage III non-small cell lung cancer.

PurposeRandomized trials showing a clear survival benefit of intensity-modulated radiotherapy (IMRT) over 3-dimensional conformal radiotherapy (3D-CRT) in the treatment of lung cancer are lacking. This study compared the survival rates of patients with stage III non-small cell lung cancer who were treated with either 3D-CRT or IMRT and analyzed the prognostic factors for survival.MethodsFrom January 2008 to July 2015, 19 patients were treated with IMRT and 30 were treated with 3D-CRT in our institution. The choice between 3D-CRT and IMRT was determined by the physician based on tumor extent and general condition of the patients. The primary endpoint of this study was overall survival. The secondary endpoints were loco-regional recurrence-free survival, distant metastasis-free survival, and the incidence of radiation-induced lung and esophageal toxicities.ResultsThe 1- and 2-year overall survival rates were 94.7% and 77.1% in the IMRT group and 76.7% and 52.5% in the 3D-CRT group, respectively. The overall survival rates of the IMRT group were higher than those of the 3D-CRT group; however, these differences were not statistically significant (P=0.072). Gross tumor volume was significantly associated with the overall survival rate. The 1- and 2-year loco-regional recurrence-free survival rates were 63.2% and 51% in the IMRT group and 67.5% and 48.1% in the 3D-CRT group (P=0.897), respectively. The 1- and 2-year distant metastasis-free survival rates were 78.9% and 68.4% in the IMRT group and 62.6% and 40.9% in the 3D-CRT group (P=0.120), respectively. Chemotherapy and treatment interruption were significantly associated with distant metastasis-free survival.ConclusionIMRT showed comparable or better overall survival compared with 3D-CRT in patients with stage III non-small cell lung cancer. To confirm the results of this study, further randomized prospective trials comparing IMRT with 3D-CRT are warranted.

Acute toxicity with intensity modulated radiotherapy versus 3-dimensional conformal radiotherapy during preoperative chemoradiation for locally advanced rectal cancer

Background and purposeWe examined acute toxicity profiles and outcomes among rectal cancer patients treated with pre-operative chemoradiation using intensity modulated radiotherapy (IMRT) or 3-dimensional conformal radiotherapy (3DCRT) to identify predictive clinical factors associated with increased acute toxicity. Material and methodsWe retrospectively reviewed records of 301 consecutive rectal cancer patients treated with pre-operative chemotherapy and radiotherapy (median dose 5000cGy) at our institution between 2007 and 2014. ResultsOf the 301 patients, 203 (67.4%) were treated with IMRT and 98 (32.6%) with 3DCRT. Significantly more patients experienced ⩾grade 2 diarrhea in the 3DCRT group compared to the IMRT group (22% vs 10%, p=0.004), and those who received 3DCRT had 2.7 times greater odds of a higher diarrhea score than those on IMRT, even after adjusting for patient characteristics and chemotherapy (OR 2.71, p=0.01) Fewer patients experienced grade 2 genitourinary toxicity in the IMRT group (6% vs 13% 3DCRT, p=0.04) and there was a trend toward decreased grade 2 proctitis in the IMRT group (22% vs 32% 3DCRT, p=0.07). Patients over the age of 55 had 45% lower odds of proctitis than patients younger than 55. ConclusionThe use of IMRT significantly reduced grade ⩾2 diarrhea and GU toxicity during chemoradiation. Younger patients were more likely to report grade 2 or higher proctitis.

Clinical Results of Definitive Chemoradiation Therapy for Cervical Esophageal Cancer: Comparison of Failure Pattern and Toxicities Between Intensity Modulated Radiation Therapy and 3-Dimensional Chemoradiation Therapy Group

Cervical esophageal cancer (CEC) is relatively uncommon disease, reported as approximately 4% of all esophageal cancer cases. To evaluate the clinical efficacy of chemo-IMRT for CEC, we retrospectively analyzed our cohort including group treated with 3DCRT. Eighty CEC patients treated with definitive chemoradiation therapy between 2002 and 2014 were entered. Histopathology of all cases was squamous cell carcinoma. Majority of patients received systemic chemotherapy using platinum agent. CTVprimary was defined as GTV with 2 cm of cranio-caudal margin. CTVprophylactic covered from cervical node of level III to the subcarina. PTV was defined as CTV with 0.5-1.5 cm margin. A total dose of 60 Gy in 30 fractions was delivered to PTV. In case of simultaneous integrated boost method of IMRT (N = 13), 48 Gy in 30 fx was delivered to PTVprophylactic. In 3D planning, 40 Gy in 20 fx was delivered to PTVprophylactic, followed by additional 20 Gy in 10 fx by 3D planning (N = 48) or IMRT (N = 19). Patient characteristics of the entire group was median age (y.o.) of 65 (41-83), male: female of 57: 23, PS 0: 1: 2 of 11: 65: 4, T category 1: 2: 3: 4 of 11: 10: 28: 31, N category 0: 1 of 18: 62, Stage I: IIA: IIB: III: IVA of 6: 7: 11: 40: 16 (clinical TNM stage UICC v.6), respectively. With a median follow-up of 24.6 M, the 2-year overall survival (OS) rate of IMRT, 3DCRT and the entire group were 81.6%, 66.1% and 72.4%, respectively. In univariate analysis, IMRT significantly associated with better OS (P = 0.037). On the other hand, there was no significant difference between two groups in both locoregional control (IMRT/3DCRT of 61.0%/63.4%, P = 0.51) and progression-free survival (IMRT/3DCRT; 45.7%/36.5%, P = 0.73), respectively. In multivariate analysis, only IMRT proved to be a favorable factor of OS (HR = 0.39 [95% CI: 0.16-0.98], P = 0.045). Between two groups there was no difference in both loco-regional progression (LRP; IMRT/3DCRT; 44%/38%, P = 0.65) and development of distant metastasis (IMRT/3DCRT; 25%/27%, P = 0.99), respectively. Ten lymph node metastases (42%) out of 24 distant metastases developed out of CTV (abdominal /neck of 3/7). Even if primary lesion did not involve to hypopharynx, cervical node recurrence out of CTV developed especially in cases of nodal involvement (6 out of 62). Six (60%) out of 10 LRPs from IMRT group successfully salvaged, while only 1 (20%) out of 5 LRPs from 3DCRT group could be rescued. As for late toxicity of G3 or more, there existed 3 of esophageal bleeding, 6 of esophageal fistula, 9 of esophageal stricture, and 1 of and pericardial effusion, respectively. Although we could not find apparent difference of efficacy between two groups, IMRT showed better OS with potentially benefit in higher salvage rate compared to that of 3DCRT. Extended cervical nodal irradiation might be considered especially in case with nodal involvement.

Technical advancement improves survival in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy

This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA-NSCLC receiving definitive radiotherapy (RT). Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival (OS), cancer specific survival (CSS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation-induced lung injury (RILI) and esophageal injury (RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 (NCI-CTCAE 3.0). A total of 946 patients were eligible for analysis, including 288 treated with two-dimensional radiotherapy (2D-RT), 209 with three-dimensional conformal radiation therapy (3D-CRT) and 449 with intensity-modulated radiation therapy (IMRT) respectively. The median follow-up time for the whole population was 84.1 months. The median OS of 2D-RT, 3D-CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5-year survival rate of 8.7%, 13.0% and 18.8%, respectively (P<0.001). The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D-RT than those provided by 3D-CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D-CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D-RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D-CRT, IMRT provided superior DMFS (P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were significantly decreased in the IMRT group (29.3% vs. 26.6% vs.14.0%, P<0.001) whereas that of RIET rates were similar (34.7% vs. 29.7% vs. 35.3%, P=0.342) among the three groups. Radiation therapy technique is a factor affecting prognosis of LA-NSCLC patients. Advanced radiation therapy technique is associated with improved tumor control and survival, and decreased radiation-induced lung toxicity.

A comparative study of distribution of residual cancer cells in the bowel wall after preoperative three-dimensional conformal radiotherapy versus volumetric modulated arc therapy with concurrent chemotherapy in treatment of locally advanced rectum cancer

Objective To compare the distribution of residual cancer cells (RCC) in each layer of bowl wall after preoperative three-dimensional conformal radiotherapy (3DCRT) versus volumetric modulated arc therapy (VMAT) combined with concurrent chemotherapy, and to investigate the effect of different radiotherapy techniques on the distribution of RCC. Methods A total of 334 patients with locally advanced rectum cancer (LARC) who were admitted to our hospital from May 2007 to April 2013 were enrolled as subjects. In those patients, 172 received preoperative 3DCRT (46 Gy/23 F) with concurrent chemotherapy and 162 received VMAT (50 Gy/25 F) with concurrent chemotherapy. There was no significant difference in the distribution of clinical stage Ⅱ or Ⅲ between the 3DCRT group and VMAT group. All the RCCs in different layers of surgical specimens were evaluated pathologically. Between-group comparison of data was made by Pearson Chi-Square and Fisher's exact test. Results There were no significant differences in ypT, ypN, or ypTNM staging between the two groups (P values>0.05). In the 226 patients with ypT2-4 disease, the proportion of RCC in the mucosa, submucosa, muscularis propria, and subserosa/perirectal fat was 34.1%, 43.8%, 73.5%, and 69.0%, respectively. In patients with ypT2-4, pN+ , cN+ , or cT4 disease, compared with the VMAT group, the 3DCRT group had significantly higher proportion of RCCs in the mucosa (47.9% vs. 18.1%, 54.5% vs. 17.2%, 39.8% vs. 15.3%, 41.3% vs. 14.3%; P=0.000, 0.001, 0.000, 0.000) and submucosa (50.4% vs. 36.2%, 56.8% vs. 27.6%, 43.0% vs.26.6%, 45.3% vs. 27.5%; P=0.032, 0.014, 0.006, 0.017). In patients with pN0 or cT3 disease, the 3DCRT group had a significantly higher proportion of RCCs in the mucosa than the VMAT group (28.1% vs. 12.9%, P=0.002; 29.5% vs. 13.2%, P=0.015). In patients with ypT2-4, pN0/pN+ , cT3/cT4, or cN0/cN+ disease, there were no significant differences in the proportion of RCCs in the muscularis propria or subserosa/perirectal fat between the two groups (P values>0.05). Conclusions After neoadjuvant chemoradiotherapy, most RCCs reside in the muscularis propria and subserosa/perirectal fat of the bowl wall. There are no significant differences in the distribution of most RCCs in the bowel wall or postoperative pathological staging between patients undergoing different radiotherapy techniques. Key words: Rectum neoplasms/three-dimensional conformal radiotherapy; Rectum neoplasms/volumetric modulated arc therapy; Rectum neoplasms/neoadjuvant chemoradiotherapy; Residual cancer cell; Pathological staging

Short-term efficacy comparison between preoperative three dimensional conformal radiotherapy and volumetric modulated arc therapy concurrently combined with chemotherapy in the treatment of locally advanced rectal carcinoma

To compare the short-term efficacy and treatment-related adverse reaction between preoperative three dimensional conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) concurrently combined with chemotherapy in the treatment of locally advanced rectal carcinoma (LARC). Clinical data of 334 patients with LARC undergoing preoperative 3D-CRT(172 cases) or VMAT(162 cases) with concurrent Xelox chemotherapy (main protocol: capecitabine plus oxaliplatin) and surgery in Sun Yat-sen University Cancer Center from May 2007 to April 2013 were retrospectively analyzed. The total radiation dose of VMAT group was: 50 Gy/2.0 Gy per fraction ×23 fractions for planning target volume 1(PTV1) and 46 Gy/1.84 Gy per fraction ×25 fractions for PTV2; the total radiation dose of 3D-CRT group was: 46 Gy/2.0 Gy per fraction ×23 fractions for PTV. The treatment-related adverse reaction of both groups during chemoradiotherapy was measured according to the criteria of Common Terminology Criteria for Adverse Events v3.0 (CTCAE 3.0). Rate of adverse reaction and short-term efficacy between 3D-CRT and VMAT group were compared, in terms of radiotherapy break, hematological and non-hematological toxicity, average duration of surgery and perioperative hospitalization, intraoperative blood loss, surgical procedures, R0 excision, sphincter preservation, postoperative complications, pathological complete response (pCR), and postoperative pathological staging. There were no significant differences in baseline clinical parameters between 3D-CRT and VMAT group (all P>0.05), except for the distance from lower tumor margin to anal verge (P=0.009). The median radiation dose for all the patients was 46 (45 to 70) Gy. There was no significant difference in the rate of radiotherapy cessation between 3D-CRT and VMAT group [1.7%(3/172) vs. 1.2%(2/162), P=1.000]. During concurrent chemotherapy, incidences of grade 2 to 3 hematological toxicities, grade 2 diarrhea, and grade 3 non-hematological toxicities were not significantly different(all P>0.05), while in grade 2 non-hematological toxicities, ratio of radiodermatitis and hand-foot syndrome was higher in VMAT group as compared to 3D-CRT group [25.9%(42/162) vs. 10.5%(18/172), P=0.000; 3.7%(6/162) vs. 0, P=0.012]. There was no grade 4 adverse event in both groups. Surgical procedure, average duration of surgery, R0 excision, anus preservation, postoperative complications, pCR, and postoperative pathological staging were not significantly different(all P>0.05). As compared to 3D-CRT group, VMAT group had less intraoperative blood loss [(114.6±100) ml vs. (169±143.9) ml, P<0.001] and shorter perioperative hospitalization [16(8 to 84) d vs. 20(10 to 47) d, P<0.001]. There was no death case in two groups within 30 days after operation. Compared with 3D-CRT technique, preoperative VMAT technique can not significantly reduce the incidence of treatment-related adverse reaction and improve the short-term efficacy in the treatment of LARC.

Hypofraction radiotherapy by helical tomotherapy for unresectable but confined intrahepatic hepatocellular carcinoma is efficient and safe in comparison with conventional 3-dimension conformal radiotherapy

Objective To evaluate the safety of helical tomotherapy (HT) for hepatocellular carcinoma confined to the liver, and to investigate the efficacy of HT by comparison with three-dimensional conformal radiotherapy (3DCRT). Methods In June 2011, hypofractionated HT was performed in 35 patients with unresectable hepatocellular carcinoma confined to the liver who had no distant metastasis or tumor thrombosis. The dose in each fraction increased from 2.4 Gy to 5.0 Gy with a median dose of 3.2 Gy. The median dose for the total treatment was 50.0 Gy. Within the same period, 45 patients received conventionally fractionated 3DCRT with a median dose of 54.0 Gy. The adverse reactions, clinical outcomes, and survival time were compared between the two groups. The survival rate was calculated with Kaplan-Meier method, and log-rank test was used to estimate statistical significance of survival differences. Multivariate analysis of survival was carried out with Cox’s regression model. Results There were no significant differences in adverse reactions between the two groups. The objective response rate was significantly higher in the HT group than in the 3DCRT group (60% vs. 33%, P=0.024). There was no significant difference in the disease control rate between the two groups (94% vs. 89%, P=0.459). The HT group showed significantly higher 1-, 2-, and 3-year overall survival rates than the 3DCRT group (97% vs. 80%, P=0.025; 81% vs. 55%, P=0.008; 67% vs. 50%, P=0.048). The multivariate analysis indicated that tumor smaller than 8 cm, transarterial chemoembolization before radiotherapy, and HT were associated with improved survival (P=0.005; P=0.000; P=0.002). Conclusions HT shows an advantage in precise treatment of hepatocellular carcinoma confined to the liver. With acceptable toxicity, hypofractionated HT shortens the treatment duration and improves the survival in patients. Key words: Liver neoplasms/radiotherapy; Radiotherapy, helicaltomo; Radiotherapy, three-dimensional conformal; Prognosis

Therapeutic effects of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with stage III N (+ ) esophageal cancer: a comparative study

Objective To investigate the therapeutic effects and adverse effects of three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅲ N (+ ) esophageal cancer. Methods A total of 428 patients with esophageal cancer who were treated from 2003 to 2012 and met the inclusion criteria were enrolled, and among these patients, 293 received 3DCRT and 135 received IMRT. The median radiation dose was 60 Gy. The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis. Results The 1-, 3-, and 5-year local control rates in 3DCRT group and IMRT group were 65.1%/40.6%/37.5% and 70.0%/57.0%/49.4%, respectively (P=0.025). The 1-, 3-, and 5-year overall survival (OS) rates in 3DCRT group and IMRT group were 56.0%/22.3%/15.7% and 53.3%/29.2%/17.8%, respectively (P=0.394). Compared with the 3DCRT group, the IMRT group had a significantly higher mean lung dose (P=0.001) and significantly lower lung V20, V25, V30, and V35(P=0.007, 0.000, 0.000, and 0.000). Compared with the 3DCRT group, the IMRT group had significantly higher incidence rates of grade Ⅱ and Ⅲ acute radiation esophagitis and grade Ⅱ acute radiation pneumonitis (P=0.000, 0.006, and 0.043). Of all patients, 343 patients died, and the main cause of death was local factors (60.6%), followed by distant metastasis (25.1%). The IMRT group had a significantly lower proportion of patients who died of local factors than the 3DCRT group (51.0% vs. 64.5%, P=0.021). Conclusions IMRT is effective in the treatment of esophageal cancer, and compared with 3DCRT, it significantly improves the local control rate. However, IMRT does not improve the long-term OS rate. The main cause of death is local factors, followed by distant metastasis. The patients receiving IMRT have a significantly lower proportion of those who die of local factors than the patients receiving 3DCRT. Key words: Esophageal neoplasms/radiotherapy; Radiotherapy, three-dimensional conformal; Radiotherapy, intensity-modulated; Prognosis

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT.

The standard treatment for stage III non-small-cell lung cancer (NSCLC) is still 60 Gy in conventional fractions combined with concurrent chemotherapy; however, the resulting local controls are disappointing. The aim of this study was to compare and assess the feasibility and efficacy of hypofractionated chemoradiotherapy using helical tomotherapy (HT) with conventional fractionation as opposed to using three-dimensional conformal radiotherapy (3D-CRT) for stage III NSCLC. Sixty-nine patients with stage III (AJCC 7th edition) NSCLC who underwent definitive radiation treatment at our institution between July 2011 and November 2013 were reviewed and analyzed retrospectively. A dose of 60 Gy in 20 fractions was delivered in the HT group (n=34), whereas 60 Gy in 30 fractions in the 3D-CRT group (n=35). Primary endpoints were toxicity, overall response rate, overall survival (OS) and progression-free survival (PFS). The median follow-up period was 26.4 months. V20 (P=0.005), V30 (P=0.001), V40 (P=0.004), mean lung dose (P=0.000) and max dose of spinal cord (P=0.005) were significantly lower in the HT group than in the 3D-CRT group. There was no significant difference in the incidences of acute radiation pneumonitis (RP) ≥ grade 2 between the two groups, whereas the incidences of acute radiation esophagitis ≥ grade 2 were significantly lower in the HT group than in the 3D-CRT group (P=0.027). Two-year overall response rate was significantly higher in the HT group than in the 3D-CRT group (P=0.015). One- and 2-year OS rates were significantly higher in the HT group (95.0% and 68.7%, respectively) than in the 3D-CRT group (85.5% and 47.6%, respectively; P=0.0236). One- and 2-year PFS rates were significantly higher in the HT group (57.8% and 26.3%, respectively) than in the 3D-CRT group (32.7% and 11.4%, respectively; P=0.0351). Univariate analysis indicated that performance status (PS), T stage and radiotherapy technique were significant prognostic factors for both OS and PFS. Multivariate analysis indicated that PS and radiotherapy technique were independent prognostic factors of OS and PS was independent prognostic factor of PFS. Hypofractionated chemoradiotherapy via HT can shorten the radiotherapy time without increasing treatment-related toxicity. The preliminary findings are that OS and PFS can be improved by hypofractionated chemoradiotherapy via HT for patients with stage III NSCLC.