Incidence Of Severe Late Toxicity Research Articles

Concurrent chemoradiotherapy with or without neoadjuvant chemotherapy in pediatric patients with stage III-IVa nasopharyngeal carcinoma: a real-world propensity score-matched cohort study.

To compare neoadjuvant chemotherapy (NAC) plus concurrent chemoradiotherapy (CCRT) to CCRT alone in children and adolescents (age ≤ 18years) with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC, stage III-IVA). 195 CA-LANPC patients who were treated through CCRT with or without NAC between 2008 and 2018 were enrolled in this study. A matched cohort composed of CCRT patients and NAC-CCRT patients was generated by propensity score matching (PSM) at a 1:2 ratio. Survival outcomes and toxicities were compared between the CCRT group and NAC-CCRT group. Of the 195 patients, 158 (81%) received NAC plus CCRT, and 37 (19%) received CCRT alone. The NAC-CCRT group had higher EBV DNA levels (≥ 4000 copy/mL), more advanced TNM stage (stage IV disease), and lower incidence of a high radiation dose (> 6600cGy) than the CCRT group. To avoid bias in treatment selection within retrospectively analysis, 34 patients from the CCRT group were matched with 68 patients from the NAC-CCRT group. In the matched cohort, the 5-year DMFS rate was 94.0% in the NAC-CCRT group versus 82.4% in the CCRT group, with marginal statistical significance (HR = 0.31; 95%CI 0.09-1.10; P = 0.055). During treatment, the accumulate incidence of severe acute toxicities (65.8% vs 45.9%; P = 0.037) in the NAC-CCRT group was higher than the CCRT group. However, the CCRT group had significantly higher accumulate incidence of severe late toxicities (30.3% vs 16.8%; P = 0.041) than the NAC-CCRT group. Addition of NAC to CCRT tended to improve long-term DMFS in CA-LANPC patients with acceptable toxicity. However, relative randomized clinical trial is still needed in the future.

Incidence of severe late toxicities of head and neck squamous cell cancer (HNSCC) treatment in the era of intensity modulated radiotherapy (IMRT).

e17570 Background: IMRT for HNSCC limits exposure to critical nearby structures thereby reducing toxicities. Real world data on toxicities after long term follow-up post IMRT for HNSCC are lacking. This study assessed the incidence of late toxicities in patients with HNSCC within 5 years post-treatment with definitive IMRT (d-IMRT). Methods: This is a retrospective, IRB approved, single-institution review of patients (pts) with stage I-IVB HNSCC treated with d-IMRT +/- chemotherapy between 2009 and 2013. The primary outcomes were incidence of severe late toxicities (dysphagia requiring esophageal stricture dilation, physician-reported grade 2 or worse neck fibrosis and xerostomia) occurring 3 months or more after completion of IMRT; feeding tube (FT) dependence within 1st year of IMRT completion, and FT dependence beyond 1st year post IMRT. Toxicities were deemed acute if they occurred during IMRT and up to 90 days post IMRT. Results: 274 pts, median age 59 years (38 – 82.9), were identified. 67.6% were HPV positive, 10.5% HPV negative and HPV status was unknown in 21.9%. Site of disease was oropharynx in 70%, larynx in 25% and hypopharynx in 4%. 206 pts (75.2%) received d-IMRT alone, 37 (13.5%) had definitive concurrent chemoradiation – mostly with cisplatin (58%), and 31 (11.3%) received adjuvant IMRT. Of the 243 pts treated with d-IMRT +/- chemotherapy, 80 (32.9%) required FT during RT due to grade 2 or worse acute dysphagia. Excluding 11 pts with disease recurrence or new HNSCC diagnosis, FT dependence at any time from 3 months to one year post IMRT occurred in 22 of 232 pts (9.48%), while FT dependence beyond 1st year post IMRT occurred in 8 pts (3.4%). 11 pts (4.7%) required stricture dilation for late dysphagia. Late grade 2 or worse fibrosis and xerostomia occurred in 7 (3.0%) and 89 (38.4%) pts, respectively. Conclusions: Our study suggests that except for xerostomia, severe late toxicities after definitive IMRT for HNSCC is likely uncommon. Prospective studies with late IMRT toxicities and their impact on quality of life (QoL) as endpoints are warranted.

What is the price of functional surgical organ preservation in local-regionally advanced supraglottic cancer? Long-term outcome for partial laryngectomy followed by radiotherapy in 32 patients.

To achieve the goal of organ preservation, both a chemoradiotherapy and a conservative surgical approach can be proposed. The aim of the study was to review all patients treated in our Institute with conservative surgery and postoperative radiotherapy for locally advanced supraglottic tumor. A retrospective analysis of 32 patients treated between 2000 and 2010 was performed. Overall survival, disease-free survival and late laryngeal toxicity were evaluated. The impact of surgical procedures, radiotherapy characteristics and addition of chemotherapy on late laryngeal toxicity was studied. The median follow-up was 38 months. Overall survival and disease-free survival at 5 years were 73% and 66%, respectively. Three (9%) patients experienced local recurrence (after 22, 25 and 40 months, respectively) and were treated with total laryngectomy. The larynx preservation rate was 93%. Severe treatment-related late laryngeal toxicity (grade 3 and 4 laryngeal edema, laryngeal stenosis, presence of tracheotomy at last follow-up because of treatment-related toxicity, and the need for enteral nutrition) was experienced by 34% of patients. The functional larynx preservation rate was 81%. The statistically significant risk factors for severe late toxicity were: female gender, extension of the surgical procedure, removal of one arytenoid and association with concomitant chemotherapy. We confirmed literature data on the feasibility and efficacy of a surgical organ preservation strategy. However, the high incidence of severe late toxicity requires further studies to improve patient selection and to reduce side effects.

Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication.

To determine the feasibility of stereotactic body radiotherapy (SBRT) in patients with pelvic sidewall recurrence of uterine cervical cancer after radical hysterectomy or definitive radiotherapy. We retrospectively reviewed 23 patients with locally recurrent uterine cervical cancer limited to the pelvic sidewall who were treated with SBRT at our institution between January 2003 and May 2010. The SBRT dose ranged from 27 to 45 Gy (median, 39 Gy) in three fractions, and the fractional SBRT dose ranged from 9 to 15 Gy (median, 13 Gy). The 2-year overall survival, local progression-free survival and disease progression-free survival rates were 43%, 65% and 52%, respectively. Patients with small tumors (gross tumor volume <30 cm(3) ) had a significantly longer 2-year overall survival rate and 2-year local progression-free survival rate than did patients with large tumors (overall survival rate: 89% vs 12%; P = 0.0001 and local progression-free survival: 85% vs 0%; P = 0.0199). There were three cases (13%) of severe toxicities (rectovaginal fistula). Pelvic pain relief was achieved in all patients. In particular, 10 of 14 patients (71%) achieved analgesic (nonsteroidal anti-inflammatory drug or narcotic) reduction of 50% or more from baseline. SBRT is a feasible treatment option for women with pelvic sidewall tumors from recurrent uterine cervical cancer, especially for small recurrent tumors. However, SBRT should be used carefully in the treatment of large tumors, as the incidence of severe late toxicity increases with the size of the tumor.

What is the price of functional surgical organ preservation in local-regionally advanced supraglottic cancer? Long-term outcome for partial laryngectomy followed by radiotherapy in 32 patients

To achieve the goal of organ preservation, both a chemoradiotherapy and a conservative surgical approach can be proposed. The aim of the study was to review all patients treated in our Institute with conservative surgery and postoperative radiotherapy for locally advanced supraglottic tumor. A retrospective analysis of 32 patients treated between 2000 and 2010 was performed. Overall survival, disease-free survival and late laryngeal toxicity were evaluated. The impact of surgical procedures, radiotherapy characteristics and addition of chemotherapy on late laryngeal toxicity was studied. The median follow-up was 38 months. Overall survival and disease-free survival at 5 years were 73% and 66%, respectively. Three (9%) patients experienced local recurrence (after 22, 25 and 40 months, respectively) and were treated with total laryngectomy. The larynx preservation rate was 93%. Severe treatment-related late laryngeal toxicity (grade 3 and 4 laryngeal edema, laryngeal stenosis, presence of tracheotomy at last follow-up because of treatment-related toxicity, and the need for enteral nutrition) was experienced by 34% of patients. The functional larynx preservation rate was 81%. The statistically significant risk factors for severe late toxicity were: female gender, extension of the surgical procedure, removal of one arytenoid and association with concomitant chemotherapy. We confirmed literature data on the feasibility and efficacy of a surgical organ preservation strategy. However, the high incidence of severe late toxicity requires further studies to improve patient selection and to reduce side effects.

Fractionated stereotactic radiotherapy for 136 patients with locally residual nasopharyngeal carcinoma

BackgroundTo evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC).MethodsFrom January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction.ResultsFive-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS.ConclusionFSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications.

Robotic system-based fractionated stereotactic radiotherapy in locally recurrent nasopharyngeal carcinoma

Purpose We reviewed survival, local control, and toxicity in patients with locally recurrent nasopharyngeal carcinoma (NPC) who had been treated with fractionated stereotactic radiotherapy (FSRT). Materials and methods Between June 2002 and March 2008, we retrospectively reviewed 35 patients with locally recurrent NPC treated using FSRT with CyberKnife. Gross tumor volumes ranged from 2.6 to 64.0 ml (median, 7.9 ml). Radiation doses were prescribed at the isodose line (75–84% of the maximum dose; median, 80%). The prescribed dose of FSRT ranged from 24 to 45 Gy (median, 33 Gy) in three or five fractions. Results The overall survival (OS) rate, local failure-free survival (LFFS) rate, and disease progression-free survival (DPFS) rate at 5 years were 60%, 79%, and 74%, respectively. Twenty-three patients achieved complete response after FSRT. Only T stage at recurrence was an independent prognostic factor for OS and DPFS. Five patients exhibited severe late toxicity (Grade 4 or 5). Conclusions With regard to OS and LFFS, our study provided favorable outcomes. The incidence of severe late toxicities was acceptable in our study. FSRT would be considered as the alternative treatment of choice in re-irradiation for locally recurrent NPC.

Intensity-Modulated Radiation Therapy in Gynecologic Cancers: Growing Support, Growing Acceptance

Since the initial report on treatment of gynecologic cancer patients with intensity-modulated radiation therapy (IMRT),1 enthusiasm for its use has steadily grown. In 2002, we performed a nationwide survey and found that 15% of IMRT users had treated at least one gynecologic patient with IMRT. 2 In our 2004 follow-up survey, this percentage had increased to 35%, making gynecology the fourth most common site treated with IMRT and the most rapidly growing IMRT site overall. 3 Given the strong motivation for the use of IMRT in gynecology patients, such enthusiasm is understandable. Conventional fields irradiate large volumes of normal tissue, including bowel, bladder, rectum, bone marrow, and femoral heads, exposing women to a wide variety of acute and late sequelae. Concerns about toxicity also limit the total radiation dose prescribed, despite potential benefits of dose escalation in women with gross residual or unresectable disease. Finally, although brachytherapy is a cornerstone of gynecologic radiotherapy, it is not feasible or optimal in all patients, and IMRT may represent a viable alternative to, or replacement for, brachytherapy. Despite these rationales, concerns exist regarding the widespread use of IMRT in gynecology patients. One relevant concern is that although many studies demonstrate the superiority of IMRT planning over conventional techniques, published outcome studies of treated patients are still sparse. Moreover, the few existing clinical studies still have short follow-up and limited information on long-term toxicities. In this issue of The Cancer Journal, Chen and colleagues4 provide important new evidence again suggesting clinical benefits of IMRT in gynecology patients. These investigators report their institutional experience with IMRT in a relatively large cohort of postoperative cervical cancer patients. Patients in this study had high-risk features after surgery and underwent adjuvant pelvic IMRT with concurrent chemotherapy and brachytherapy. IMRT plans were highly conformal, resulting in excellent target coverage and sparing of surrounding normal tissues. IMRT was well tolerated in all patients, with minimal acute genitourinary and gastrointestinal toxicity. More importantly, however, these women had an excellent long-term pelvic control (3-year locoregional control, 93%) and a low incidence of severe late toxicity (1 grade 3 genitourinary and no grade 3 gastrointestinal toxicity). This study represents an important contribution to the gynecologic IMRT literature and, together with other recent reports focusing on tumor control and long-term toxicity, 5,6 provides further evidence that improved dosimetry of IMRT translates into clinically significant benefits.

Phase II trial: concurrent radio-chemotherapy with weekly docetaxel for advanced squamous cell carcinoma of head and neck

Standard fractionation radiation therapy (RT) combined with concomitant chemotherapy (CT) based on cisplatin schemes is actually the standard treatment for locally advanced non-resectable squamous cell carcinoma of head and neck (SCCHN). The appearance of taxoids has introduced a new kind of treatment with high antitumoral power. The aim of this study is to add more information about the role of this new approach. Twenty-six patients with locally advanced non-resectable SCCHN were recruited at six institutions in Spain, between January 2001 and January 2003. Docetaxel was administered weekly, for 6 weeks, concurrently with RT. The mean total delivered dose of RT was 70'2 Gy (range 64-74 Gy). The median and mean duration of time were 63 days and 61 days (range 49-103 days) respectively. After a median time control of 19 months (range 3.3-42.2 months), the response rate was 83.4%. The median time to local progression was 16.4 months (95% confidence interval [CI]=4.4-28.4 months). The median survival time was 26.9 months, with one- and two-year overall survival of 66.9% (95% CI=48.1-85.7%) and 57.5% (95% CI=37.3-77.7%) respectively. The median duration time response was 15.1 months (95% CI=3.7-26.5 months). The median time until treatment failure was 9.4 months (95% CI=4.7-14.1). Incidence of grade III-IV mucositis was 88%, neutropenia 72% and skin toxicity 92% (24% grade III-IV). The incidence of severe late toxicity (grade III and IV) due to RT/CT was 31.4%. Although therapeutics results are equivalent to cisplatin schemes of concurrent CT-RT, mucositis and cutaneous toxicity registered in this trial must be considered as limiting factors to application of this new approach.

Results of radiotherapy alone in the treatment of carcinoma of uterine cervix: a retrospective analysis of 1069 patients

Carcinoma of the uterine cervix is the most common malignancy affecting women in developing countries like India. This retrospective study was made to analyze our results of radiotherapy alone in the treatment of carcinoma cervix. Between January 1996 and December 2001, 1069 patients of carcinoma cervix were treated at our center with external beam radiotherapy (EBRT) and intracavitary radiotherapy (871) or EBRT alone (198). The median dose to point A was 81 Gy. Overall survival (OS), disease-free survival (DFS), and pelvic control at 5 years were 51.8%, 49.4%, and 63.9%, respectively. For the patients who could receive intracavitary radiotherapy (871), the OS, DFS, and pelvic control rates were 60.7%, 58.6%, and 73.5%, respectively. On multivariate analysis, bulk, overall treatment time (OTT) and response to EBRT were found to affect OS and DFS independently. Similarly, OTT, response to EBRT, stage, and age were the factors that influenced pelvic control. Incidence of severe late toxicities (grade 3/4) in the rectum, bladder, small intestine, and skin were 1.1%, 1.2%, 0.2%, and 1.2%, respectively. In developing countries like India, where chemoradiation can be afforded by a minority only, judicious use of radiotherapy still produces satisfactory results with acceptable toxicity. The addition of chemotherapy may be beneficial in patients with adverse prognostic factors.