Role of IMRT/VMAT-Based Dose and Volume Parameters in Predicting 5-Year Local Control and Survival in Nasopharyngeal Cancer Patients.
ABSTRACT: Objective: This study aimed to look into the relationship between intensity-modulated-radiotherapy (IMRT)- or volumetric-modulated-arc-therapy (VMAT)-based dose-volume parameters and 5-year outcome for a consecutive series of non-metastatic nasopharyngeal cancer (NPC) patients (pts) treated in a single institution in a non-endemic area in order to identify potential prognostic factors. Materials and methods: A retrospective analysis of consecutive non-metastatic NPC pts treated curatively with IMRT or VMAT and chemotherapy (CHT) between 2004 and 2014 was conducted. One patient was in stage I (0.7%), and 24 pts (17.5%) were in stage II, 38 pts (27.7%) in stage III, 29 pts (21.2%) in stage IVA, and 45 pts (32.8%) in stage IVB. Five pts (3.6%) received radiotherapy (RT) alone. Of the remaining 132 pts (96.4%), 30 pts (21.9%) received CHT concomitant to RT, and 102 pts (74.4%) were treated with induction CHT followed by RT-CHT. IMRT was given with standard fractionation at a total dose of 70 Gy. Clinical outcomes investigated in the study were local control (LC), disease-free survival (DFS), and overall survival (OS). Kaplan-Meier (KM) analysis was performed for the outcomes considering dose and coverage parameters, staging, and RT technique. Results: Overall, 137 pts were eligible for this retrospective analysis. With a median follow-up of 70 months (range 12-143), actuarial rates at 5 years were LC 90.4, DFS 77.2, and OS 82.8%. For this preliminary study, T stage was dichotomized as T1, T2, T3 vs. T4. At 5 years, the group T1-T2-T3 reported an LC of 93%, a DFS of 79%, and an OS of 88%, whereas T4 pts reported LC, DFS, and OS, respectively, of 56, 50, and 78%. Pts with V95% > 95.5% had better LC (p = 0.006). Pts with D99% > 63.8 Gy had better LC (p = 0.034) and OS (p = 0.005). The threshold value of 43.2 cm3 of GTVT was prognostic for LC (p = 0.016). To predict the risk of local recurrence at 5 years, we constructed a nomogram which combined GTVT with D99% relative to HRPTV. Conclusions: We demonstrated the prognostic value of some dose-volume parameters, although in a retrospective series, this is potentially useful to improve planning procedure. In addition, for the first time in a non-endemic area, a threshold value of GTVT, prognostic for LC, has been confirmed.
Project description:Background:The aim of the study was to investigate the feasibility and safety of experimental fractionation using intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) to shorten the overall treatment time without dose escalation in preoperative radiochemotherapy of locally advanced rectal cancer. Patients and methods:Between January 2014 and November 2015, a total of 51 patients with operable stage II-III rectal adenocarcinoma were treated. The preoperative treatment with intensity modulated radiation therapy (IMRT) and a pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumour in 22 fractions, with standard concomitant capecitabine, was completed in 50 patients out of whom 47 were operated. The median follow-up was 35 months. Results:The rate of acute toxicity G ? 3 was 2.4%. The total downstaging rate was 89% and radical resection was achieved in 98% of patients. Pathologic complete response (pCR) was observed in 25.5% of patients, with 2-year local control (LC), disease free survival (DFS), and overall survival (OS) of 100% for this patient group. An intention-to-treat analysis revealed pN to be a significant prognostic factor for DFS and OS (P = 0.005 and 0.030, respectively). LC for the entire group was 100%, and 2-year DFS and OS were 90% (95 % CI 98.4-81.6) and 92.2% (95% CI 99.6-84.7), respectively. Conclusions:The experimental regime in this study resulted in a high rate of pCR with a low acute toxicity profile. Excellent early results translated into encouraging 2-year LC, DFS, and OS.
Project description:Curative treatment for base-of-tongue squamous cell carcinoma (BOT SCC) has evolved over time; however, comparative outcomes analysis for various treatment strategies is lacking. The authors reviewed the evolution of treatment modality and radiotherapy (RT) technique for 231 consecutive BOT SCC patients at our institution between 1981 and 2011. Treatment modalities included definitive chemoradiotherapy (chemoRT) (42%), definitive RT (33%), surgery followed by RT (20%), and surgery alone (5%). RT techniques included external beam plus interstitial brachytherapy (EBRT + IB) (37%), conventional EBRT (29%), intensity-modulated radiation therapy ± simultaneous integrated boost (IMRT ± SIB) (34%). Clinical characteristics and outcomes were stratified by modality or RT technique. Treatment modality evolved from definitive RT (1980s-1990s) to definitive chemoRT (1990s-2000s). RT technique evolved from EBRT + IB (1980s-1990s) to conventional EBRT (1990s-2000s) to IMRT + SIB (2000s). With median alive follow-up of 6 years (0.3-28 years), the 5-year LC, LRC, and OS rates were 80%, 73%, and 51%. There was no difference in distribution of gender, age, stage among treatment modalities. Definitive chemoRT had improved LRC (HR 1.6) and OS (HR 1.7) compared to definitive RT. IMRT + SIB had improved LRC (HR 3.2), DFS (HR 3.4), and OS (HR 3.0) compared to conventional EBRT. Over the past 30 years, BOT SCC treatment has undergone major paradigm shifts that incorporate nonsurgical functional preservation, concurrent chemotherapy, and advanced RT techniques. Excellent locoregional control and survival outcomes are associated with accelerated IMRT with chemotherapy.
Project description:<b>Purpose:</b> To evaluate treatment outcomes and toxicity in patients with cervical cancer (CC) treated with volumetric modulated arc therapy (VMAT), followed by three-dimensional high-dose-rate intracavity combined with interstitial brachytherapy (IC/IS BT) compared with intensity-modulated radiation therapy (IMRT) treatment. <b>Materials and Methods:</b> A total of 398 patients with stage IA-IVB CC treated with definitive radiotherapy with or without chemotherapy were retrospectively analyzed (331 VMAT and 67 IMRT). A total prescription dose of 45-50 Gy was delivered to pelvic field with VMAT/IMRT in 25/28 fractions, with five fractions per week. Every patient further received IC/IS BT for four to six 6.0-Gy fractions. Local control (LC), disease-free survival (DFS), overall survival (OS), and distant metastasis-free survival (DMFS) rates were calculated. Acute hematotoxicity and late toxicity were recorded. <b>Results:</b> The median follow-up period was 25.47 (range, 0.93-58.93) months for the VMAT and 35.07 (4.8-90.37) months for IMRT. The 3-year OS, DFS, LC, and DMFS rate were 80.5, 65.4, 88.7, and 78.1% in VMAT group, and 76.2, 76.4, 83.1, and 86.1% in the IMRT group, respectively. No significant differences were found between VMAT and IMRT groups for OS, DFS, LC, and DMFS rate. However, patients in the VMAT group had lower incidence of chronic enterocolitis complication (26.6 vs. 38.8%, <i>p</i> = 0.004). In addition, a total of 3 (0.9%) patients developed grade 3 chronic cystitis, and 7 (2.1%) patients developed grade 3 or greater chronic enterocolitis in VMAT group. <b>Conclusion:</b> VMAT combined with IC/IS BT can result in satisfactory curative outcomes and low incidences of late radiation enterocolitis and cystitis in CC treatment.
Project description:Epithelial-mesenchymal transition (EMT) plays a key role in tumor metastasis, but the significance of EMT phenotype to the prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. We used immunohistochemistry to examine the expression of the EMT-related proteins E-cadherin, N-cadherin and vimentin in samples of T3N1-3M0 ESCC from 155 primary tumors (PTs) with paired metastatic lymph nodes (MLNs) and 58 PTs without paired MLNs. Based on the expression pattern of the EMT markers, PTs and MLNs were classified as EMT wild, hybrid, null or complete type. The hybrid (42.7%) and complete (39.4%) types predominated among PTs, whereas the wild (34.2%) and hybrid (52.9%) types predominated among MLNs, and EMT phenotypes differed between the paired PTs and MLNs (P < 0.001). Univariate analysis revealed that, for PTs, the EMT phenotype was associated with N-stage (P = 0.039) but not patient survival, and that patients with complete or hybrid type MLNs had better overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.005) than patients with null and wild type MLNs, especially those with N1-stage disease (P = 0.017 for OS, and P = 0.017 for DFS, respectively). Multivariate analysis revealed that wild and null type MLNs as well as older age and N2-3 stage were independent predictors of OS and DFS (P < 0.05). Thus MLNs exhibit EMT phenotypes that are distinct from those of their PT and may serve as a novel independent prognostic indicator in ESCC.
Project description:PURPOSE:The benefits of reirradiation for head and neck cancer (HNC) have not been determined. This study evaluated the efficacy of reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent or second primary HNC (RSPHNC) and identified subgroups for whom reirradiation for RSPHNC is beneficial. Materials and Methods:A total of 118 patients from seven Korean institutions with RSPHNC who underwent IMRT-based reirradiation between 2006 and 2015 were evaluated through retrospective review of medical records. We assessed overall survival (OS) and local control (LC) within the radiotherapy (RT) field following IMRT-based reirradiation. Additionally, the OS curve according to the recursive partitioning analysis (RPA) suggested by the Multi-Institution Reirradiation (MIRI) Collaborative was determined. RESULTS:At a median follow-up period of 18.5 months, OS at 2 years was 43.1%. In multivariate analysis, primary subsite, recurrent tumor size, interval between RT courses, and salvage surgery were associated with OS. With regard to the MIRI RPA model, the class I subgroup had a significantly higher OS than class II or III subgroups. LC at 2 years was 53.5%. Multivariate analyses revealed that both intervals between RT courses and salvage surgery were prognostic factors affecting LC. Grade 3 or more toxicity and grade 5 toxicity rates were 8.5% and 0.8%, respectively. CONCLUSION:IMRT-based reirradiation was an effective therapeutic option for patients with RSPHNC, especially those with resectable tumors and a long interval between RT courses. Further, our patients' population validated the MIRI RPA classification by showing the difference of OS according to MIRI RPA class.
Project description:Purpose: To explore the efficacy of concomitant chemotherapy in intensity-modulated radiotherapy (IMRT) to treat stage II nasopharyngeal carcinoma (NPC). Methods and Materials: In this randomized phase 2 study [registered with ClinicalTrials.gov (NCT01187238)], eligible patients with stage II (2010 UICC/AJCC) NPC were randomly assigned to either IMRT alone (RT group) or IMRT combined with concurrent cisplatin (40 mg/m2, weekly) (CCRT group). The primary endpoint was overall survival (OS). The second endpoints included local failure-free survival (LFFS), regional failure-free survival (RFFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and acute toxicities. Results: Between May 2010 to July 2012, 84 patients who met the criteria were randomized to the RT group (n = 43) or the CCRT group (n = 41). The median follow-up time was 75 months. The OS, LFFS, RFFS, DFS, and DMFS for the RT group and CCRT group were 100% vs. 94.0% (p = 0.25), 93.0% vs. 89.3% (p = 0.79), 97.7% vs. 95.1% (p = 0.54), 90.4% vs. 86.6% (p = 0.72), and 95.2% vs. 94.5% (p = 0.77), respectively. A total of 14 patients experienced disease failure, 7 patients in each group. The incidence of grade 2 to 4 leukopenia was higher in the CCRT group (p = 0.022). No significant differences in liver, renal, skin, or mucosal toxicity was observed between the two groups. Conclusion: For patients with stage II NPC, concomitant chemotherapy with IMRT did not improve survival or disease control but had a detrimental effect on bone marrow function.
Project description:The aim of the study was to compare incidences of late gastrointestinal adverse events and clinical outcomes between 3D conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) after radical hysterectomy for cervical cancer patients. Between March 2007 and May 2014, 73 cervical cancer patients with high-risk prognostic factors (pelvic lymph node metastasis and/or parametrial invasion) underwent postoperative pelvic radiation therapy (RT) after radical hysterectomy. Of these patients, 33 (45%) and 40 (55%) received 3DCRT and IMRT, respectively. Because the gastrointestinal obstruction rate after postoperative pelvic 3DCRT was high, no concurrent chemotherapy was applied until 2015. The median follow-up period for patients with 3DCRT and IMRT was 82 months (6-113) and 50 months (5-74), respectively. There was no significant difference in overall survival (OS) (4-year OS: 85% vs 78%, P = 0.744) or disease-free survival (DFS) (4-year DFS: 73% vs 64%, P = 0.696) between the two groups. Eleven (33%) and 13 (33%) patients experienced recurrence after 3DCRT and IMRT, respectively. The patients who had vaginal invasion from the postoperative pathological finding more frequently had loco-regional recurrence than the patients who did not have vaginal invasion (2.3% vs 17%, P = 0.033). Gastrointestinal obstruction was observed in 9 (27%) and 3 (7.5%) patients for 3DCRT and for IMRT, respectively (P = 0.026). Severe gastrointestinal obstruction that required surgery was observed in 6 (19%) patients, all of whom received adjuvant RT by 3DCRT. IMRT could reduce the incidence of late severe gastrointestinal obstruction after postoperative pelvic RT with a non-inferior clinical efficacy compared with 3DCRT.
Project description:BACKGROUND:Intensity-modulated radiotherapy (IMRT) provides excellent local control in nasopharyngeal carcinoma (NPC). We investigated whether simplifying 8th American Joint Committee on Cancer staging system T categories improves prognostic value. METHODS:We used 2191 NPC patients as a training set and 414 patients separately as an independent, external validation cohort. RESULTS:In the training set, local relapse-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were not significantly different between the 8th edition T2/T3 (P = 0.610, 0.380 and 0.353, respectively). Merging T2 and T3 to proposed T2 (proT2) provided significant differences in LRFS, DFS, and OS between proposed T categories. Proposed T categories had similar c-indices for LRFS, DFS, and OS (vs the 8th edition), which was validated in the external cohorts. Moreover, for DFS, the adjusted HRs of the proT2N0 (3.8), proT1N1 (3.8), and proT2N1 (6.0) subsets were similar; the adjusted HRs of the proT3N0 (7.0), proT3N1 (11.4), proT1N2 (11.0), proT2N2 (11.6), and proT3N2 (13.3) subsets were similar; the adjusted HRs of the proT1N3 (17.8), proT2N3 (15.3), and proT3N3 (26.4) subsets were similar; the results of the adjusted HRs for OS had the same rule. Defining proT1N0 as stage I; proT1N1/proT2N0-1 as stage II; proT3N0-2/proT1-2N2 as stage III; and proT1-3N3 as stage IVa generated orderly, significant differences in DFS and OS between stages in the training set and external validation cohort. CONCLUSIONS:In the IMRT era, three T categories are more reasonable (merging T2/T3 into T2) and proT3N0-2 (the 8th edition T4N0-2) should be down-staged to stage III.
Project description:This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m(2) and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation.
Project description:To evaluate the rationality and limitations of the seventh edition of the American Joint Committee on Cancer (the 7th AJCC edition) T-staging system for locally advanced nasopharyngeal carcinoma (NPC). The prognosis of 358 patients with stage T3/T4 NPC treated with intensity-modulated radiotherapy (IMRT) was analyzed with the Kaplan-Meier method or the log-rank test. The 7th AJCC staging system of NPC has some limitations in that the T category is neither the significant factor in OS/LRFS nor the independent prognostic factor in OS/LRFS/DMFS/DFS (P > 0.05). After adjustment by anatomic structures, univariate analysis has shown that the adjusted-T category has statistical significance between T3 and T4 for OS (86.4% and 71.3%, P = 0.002), LRFS (97% and 90.9%, P = 0.048), DMFS (90.9% and 77.2%, P = 0.001), and DFS (86.2% and 67.5%, P = 0.000), and multivariate analysis has shown that the adjusted-T category is an independent prognostic factor for OS/DMFS/DFS (with the exception of LRFS). Then, GTV-P was taken into consideration. Multivariate analysis showed that these nT categories serve as suitable independent prognostic factors for OS/DMFS/DFS (P < 0.001) and LRFS (HR = 3.131; 95% CI, 1.090-8.990; P = 0.043). The 7th AJCC staging system has limitations and should be improved by including the modifications suggested, such as anatomic structures and tumor volume adjustment.