Three-year Locoregional Control Research Articles

Definitive Chemoradiotherapy for Salivary Gland Cancers

Surgical resection is the standard of care for salivary gland tumors of the head and neck. The role of radiotherapy is typically reserved for the adjuvant setting in those patients with high risk factors on surgical pathology. Surgical resection in some cases may lead to significant impairment in speech or swallowing due to location of the primary tumor. In other cases, patients may not be medically able to receive an oncologic resection. Our institution has developed a protocol for organ preservation for well-selected salivary gland malignancies. Here we report disease outcomes of salivary gland cancer patients treated with definitive chemoradiotherapy. We retrospectively reviewed all salivary gland cancer patients at our institution who received definitive chemoradiation from January 1990 to December 2019. Chemoradiation typically consisted of 4 to 6 alternating weekly cycles of paclitaxel (100 mg/m2 on d1), infusion 5-fluorouracil (600 mg/m2/d on d0-5), hydroxyurea (500 mg PO BID), and either 1.8 Gy or 2 Gy daily or 1.5 Gy twice-daily irradiation followed by a 9-day treatment break (TFHX). The Kaplan-Meier method was used to estimate rates of locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). Nineteen patients met eligibility criteria and were included for analysis. 53% of patients had adenoid cystic histology. Salivary duct, mucoepidermoid, acinic cell, and myoepithelial histologies each were represented by 10.5% of patients. About 26% of tumors were located in the nasopharynx, 21% in the base of tongue and 26% in the parotid. 74% of the patients were node negative and 53% of patients had stage IVA disease. T3 disease occurred in 26.3% while T4a and T4b disease occurred in 31.6% each. Median follow-up was 45.8 (IQR: 29-66) months. 47% of patients were treated using a twice daily approach, while 53% were treated with daily fractionation with a median dose of 72 Gy (IQR: 70-75). Three-year locoregional control (LRC), distant-metastasis free survival (DMFS), and overall survival (OS) were 93%, 76%, and 81% respectively. Eight of nine distant failures had T4a/T4b disease. Accounting for competing risk of death, local failure was 5.6% at three years. The most common acute complications were grade 2-3 mucositis (74%) and skin toxicity (47%). One patient discontinued chemoradiation due to severe hand foot mouth syndrome. 42% of patients had late toxicity of xerostomia. Promising organ preservation is seen with concurrent chemoradiation for salivary gland cancer patients. Further prospective study of organ preservation in salivary gland cancers is warranted.

In-Field Toxicity Analysis of a Phase 1 Clinical Trial of Nivolumab and Ipilimumab With Definitive Radiation Therapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Combined modality therapy for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is associated with increased toxicities. Immunotherapy has a documented benefit in the recurrent/metastatic setting with a favorable toxicity profile. We evaluated in-field toxicities in the context of a single-institution clinical trial with combined nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, and concurrent radiation therapy (RT) in patients with LA SCCHN. We analyzed in-field toxicity events in 24 cisplatin-eligible patients with newly-diagnosed LA SCCHN (14 HPV-positive oropharyngeal) treated with nivolumab (3 mg/kg every two weeks for 17 doses) and ipilimumab (1 mg/kg every six weeks for 6 doses) starting two weeks prior to intensity-modulated radiation therapy (IMRT; 70 Gy in 2 Gy fractions). All patients completed RT with no treatment delays. 16/24 patients experienced at least one grade 3 in-field toxicity during radiation treatment including radiation dermatitis (5), dysphagia (6), oral mucositis (10), odynophagia (3), oropharyngeal pain (1), and hoarseness (1). There were no grade 4 or 5 AEs during ICI-RT. Five patients (22%) developed soft tissue ulcers (STU) at the primary tumor site during the consolidation phase, one of which led to a fatal carotid rupture. STUs developed at a median of 91 (range 50-107) days post RT and were negative for viable tumor. Three-year locoregional control rate was 94.7% (95% CI, 85.2%-100%). Concurrent radioimmunotherapy with nivolumab and ipilimumab resulted in excellent locoregional control, but may have an increased the risk of STU. Patients treated with such an approach should be closely monitored for in-field toxicity events, including soft tissue ulceration.

Timing of radiotherapy and chemotherapy start for patients treated with definitive concurrent chemoradiation for head and neck cancer

Background The ideal timing for the initiation of chemotherapy and radiation therapy (RT) in the use of definitive chemoradiation (CRT) for patients with head and neck cancer is not well established. We sought to evaluate the impact of the timing of initiating these two modalities on clinical outcomes. Materials and methods Patients with squamous cell carcinoma of the head and neck who were treated using definitive chemoradiation from 2012 to 2018 were identified. Patients undergoing re-irradiation, post-op CRT, had recurrent or second primaries, or ECOG 3-4 were excluded. Outcomes including locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated and compared between subgroups of the cohort based on the timing in which chemotherapy or RT were initiated: chemotherapy first, same day start, within 24 h, or start on Monday/Tuesday/Wednesday. Results A total of 131 patients were included for analysis consisting of oropharynx (64%), larynx (22.9%), nasopharynx (6.9%), hypopharynx (3.1%), oral cavity (1.5%), and unknown primary (1.5%). Chemotherapy was administered as bolus cisplatin every 3 weeks in 40% of patients and weekly cisplatin in 60% with a median cumulative dose of 240 mg/m2. In the multivariable analysis (MVA), starting chemotherapy before RT was associated with improved LRC (HR 0.33, 95% CI: 0.11–0.99). Three-year LRC for patients starting chemotherapy first was 90.9% compared to 78.2% in those starting RT first. In the MVA, cisplatin regimen and cumulative cisplatin dose were associated with improved OS, while no factors were significantly associated with DC or PFS. Conclusion Starting chemotherapy prior to radiation therapy improves LRC, but did not impact DC, PFS, or OS. Clinical outcomes were not different when stratifying by the other differences in the timing of initiating chemotherapy or RT.

Quality of life score as a prognosticator for pharyngeal cancer patients treated with radiotherapy

The purpose of this study was to evaluate the prognostic value of quality of life (QOL) scores acquired not only pre-treatment, but also 1 month after treatment for locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with pharyngeal cancer treated using radiotherapy. Data for 102 patients with naso-, oro-, or hypo-pharyngeal cancer treated between December 2008 and September 2017 were retrospectively analyzed. About 90% of the patients were male. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was used for QOL assessments. Associations between QLQ-C30 scores before and 1 month after treatment and outcomes including LRC, DMFS, and OS were analyzed using Cox proportional hazard models. Median follow-up was 37 months (range, 5–117 months). Three-year LRC, DMFS, and OS rates were 77.8%, 60.0%, and 66.5%, respectively. Pre-treatment emotional functioning and diarrhea at 1 month after treatment were identified as significant predictors of LRC. Pre-treatment global QOL and diarrhea at 1 month after treatment were detected as significant predictors of DMFS. Pre-treatment emotional functioning, pre-treatment appetite loss, and diarrhea at 1 month after treatment were detected as significant predictors of OS. Diarrhea at 1 month after treatment was the most powerful QOL variable for predicting LRC, DMFS and OS. Our study revealed that several QOL scores not only before treatment but also 1 month after treatment correlated with LRC, DMFS and OS. In particular, the diarrhea domain of QOL at 1 month after treatment offered the most powerful prognosticator for pharyngeal cancer patients treated with radiotherapy.

Post-operative re-irradiation with hyperthermia in locoregional breast cancer recurrence: Temperature matters

PurposeTo investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia. MethodsIn this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010–2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4–5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into ‘low’ (n = 56) and ‘high’ TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed. ResultsTD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1–107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2–60.2), lymph node involvement (HR 2.9; 95%CI 1.2–7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8–11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4–11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018). ConclusionsHigh thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity.

Outcome of chemoradiotherapy using intensity-modulated radiation therapy for cervical esophageal cancer: a single institute experience.

The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated. Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60Gy and concurrent platinum-based doublet chemotherapy. The median follow-up period for surviving patients was 36months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival. Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.

Pathological responses to low-dose irradiation and Pepleomycin in Oral squamous cell carcinoma are predictive of Locoregional control

BackgroundThe prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence.MethodsWe retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3–4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato.ResultsEight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively.ConclusionsThe present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.

Chemoradiotherapy using retrograde superselective intra-arterial infusion for tongue cancer: Analysis of therapeutic results in 118 cases

ObjectivesTo evaluate the therapeutic results and rate of organ preservation in patients with squamous cell carcinoma of the tongue treated with retrograde superselective intra-arterial chemoradiotherapy. Materials and methodsBetween June 2006 and June 2015, 118 patients with tongue cancer were treated with intra-arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50–70 Gy) and daily concurrent intra-arterial chemotherapy (docetaxel, total 50–70 mg/m2; cisplatin, total 125–175 mg/m2) for 5–7 weeks. Locoregional control and overall survival rates were calculated by the Kaplan-Meier method. Cox’s proportional hazards model was used for both univariate and multivariate analyses. ResultsThe median follow-up for all patients was 38.5 months (range, 3–129 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in 45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients. On univariate analysis, T stage and overall stage were significantly associated with locoregional control, and N stage and overall stage were significantly associated with overall survival. On multivariate analysis, the only significant predictor of overall survival was overall stage classification. ConclusionRetrograde superselective intra-arterial chemoradiotherapy for tongue cancer provided good overall survival and locoregional control.

Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control

BackgroundEndoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment after ESD is needed to prevent lymph node metastasis. However, the efficacy of radiotherapy following ESD has not been well evaluated. Moreover, the clinical outcomes of patients with large mucosal defects of the esophagus who received radiotherapy after ESD have not been reported. This study aimed to clarify the efficacy of additional radiotherapy following ESD for esophageal squamous cell cancer involving T1a-MM or T1b-SM1.MethodsWe analyzed twenty-seven patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer treated by ESD. Thirteen patients received additional radiotherapy (RT group), and the remaining patients did not (non-RT group). Locoregional control (LRC), overall survival, cause-specific survival, and adverse events including treatment-related esophageal strictures were evaluated.ResultsThe three-year LRC was significantly better for the RT than the non-RT group (100% vs. 57.8%, respectively; p = 0.022). Chemotherapy following ESD did not improve LRC. Multivariate analysis showed that radiotherapy was an independent prognostic factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and cause-specific survival were not significantly different between the RT and non-RT groups. A subgroup analysis of patients with mucosal defects involving ≥ 3/4 of the esophageal circumference after ESD showed that LRC of the RT group was better than that of the non-RT group (p = 0.049). Treatment-related esophageal strictures were observed in 2 of 6 patients in the RT group with large mucosal defects after ESD. No patients with mucosal defects involving less than 3/4 of the circumference after ESD developed treatment-related strictures.ConclusionsRadiotherapy after ESD contributed to better LRC in esophageal squamous cell cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in some patients with large mucosal defects after ESD. Despite leading to better LRC, radiotherapy after ESD should be undertaken after careful consideration for patients with large mucosal defects after ESD.

Predictors of prolongation in radiation treatment time in a veteran population treated with chemoradiation for oropharyngeal cancer

Background: Prolonged radiation treatment time (RTT) is associated with worse tumor control. Here we identify and determine the implications of factors that predict treatment prolongation in Veterans Affairs (VA) patients undergoing chemoradiation.Methods: Chart review from July 2000 to October 2013. 81 patients with advanced stage oropharyngeal cancer treated with chemoradiation.Results: Twenty-nine patients (35.8%) had RTT prolonged by ≥10 days. Prolongation mainly resulted from acute treatment toxicity (n = 22, 76%). There was no significant difference in RTT for patients treated with concurrent cisplatin versus cetuximab, or in patients treated with or without induction chemotherapy. One-/three-year locoregional control and overall survival rates of 83.4%/76.3% and 83.5%/63.6% for patients without prolonged RTT versus 61.8%/61.8% and 82.8%/73.8% for those with prolongation (p >.05).Conclusions: Prolonged RTT is a significant predictor of worse locoregional control and predominantly resulted from treatment side effects. More aggressive regimens with induction and concurrent chemotherapy did not predispose to prolonged RTT.

Association of Lymphovascular Space Invasion With Locoregional Failure and Survival in Patients With Node-Negative Oral Tongue Cancers

The indications for adjuvant therapy in resected oral tongue cancers are based on both clinical and pathological factors, with clear evidence for adjuvant radiation in patients with pathologically positive neck lymph nodes, positive margins, and extracapsular extension, but the data for patients with no nodal disease are sparse. To investigate determinants of failure and survival in patients with node-negative oral tongue cancer. Medical records for patients with oral tongue cancer treated with definitive surgery from 2003 to 2013 were reviewed. All patients were cN0 negative and classified as pathologically node-negative (pN0) if a neck dissection was performed. Patients received adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) based on standard clinical and pathological determinants. Kaplan-Meier and multivariable (MVA) logistic regression and Cox proportional hazard regression analyses were performed to identify patient, tumor, and treatment characteristics predictive of locoregional control (LRC) and overall survival (OS). A total of 180 patients met entry criteria, with a median follow-up time of 4.9 years (range, 0.9-12.5 years); 102 patients (56.7%) were female and 42 patients (23.3%) were younger than 45 years at diagnosis. One hundred fifty-three patients (85%) had T1/T2 tumors, and 112 patients (62%) had elective neck dissections with confirmed pN0. Lymphovascular space invasion (LVSI) was present in 36 patients (20%). On MVA, LVSI (OR, 0.06; 95% CI, 0.02-0.19; P < .01) was associated with worse LRC. Elective neck dissection (odds ratio [OR], 2.99; 95% CI, 1.16-7.73; P = .02) and receipt of RT (OR, 7.74; 95% CI, 2.27-26.42; P < .01) were associated with improved LRC. Three-year LRC rates were significantly lower for patients with LVSI (38.8%; 95% CI, 22.8%, 54.6%) than those without LVSI (81.9%; 95% CI, 74.4%, 87.4%). On MVA, only LVSI (hazard ratio, 2.20; 95% CI, 1.19-4.06; P = .01) and age greater than 44 years (hazard ratio, 4.38; 95% CI, 1.34-14.27; P = .01) were associated with worse OS. Three-year OS rates were significantly lower in patients with LVSI (71.3%; 95% CI, 53.2%-83.4%) than those without LVSI (90.3%; 95% CI, 83.8%-94.3%). Lymphovascular space invasion in patients with node-negative oral tongue cancer treated with upfront definitive surgery is associated with worse LRC and OS. Node-negative oral cavity cancers with LVSI warrant consideration of further adjuvant therapy, which should be further evaluated in a prospective setting.

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation Therapy for Locoregionally Advanced Head and Neck Cancer: HPV-negative Subset Analysis

detection of recurrence were abstracted. Patients either received definitive RT alone (nZ38, 15.4%) or concurrent systemic therapy and RT (nZ209, 84.6%). Outcomes, including local control (LC), regional control (RC), locoregional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were calculated according to Kaplan-Meier method from the end of RT. Patients received a 3-month posttreatment positron emission tomographic/computed tomographic (PET/CT) scan and were seen every 3 months in the first year, every 4 months in Year 2, and every 6 months in Years 3 to 5. Results: Median follow-up of all patients was 36 months. LC was achieved in 239 of 245 patients, with a 3-year LC rate of 97.8%. Of the 6 local failures, all were detected by direct visualization (nZ2) or flexible laryngoscopy (nZ4). Three-year RC was 95.3%, where patients with 5 nodes or level 4 lymph nodes present were more likely to suffer regional failure (P<.05). Of the 9 regional recurrences, 89% (nZ8) were found by symptoms or 3-month posttreatment PET/CT. Three-year LRC was 94%. Of the 13 patients that suffered a locoregional failure, 92% (nZ12) presented with either symptoms or persistent disease on 3-month posttreatment PET/CT. Three-year FFDM rate was 91.4%, with increased risk of metastases occurring in patients with a lymph node greater than 6 cm, bilateral lymphadenopathy, 5 or more nodes, or if a lymph node was present in level 4 (P<.05). Of the 21 patients who suffered distant recurrence, 71% (nZ15) were found due to symptoms or 3-month posttreatment imaging. Three-year OS was 91% for all patients. Late grade 3 toxicity occurred in 21 patients (9%), with 19 being grade 3 toxicities and 2 grade 4 toxicities. The majority of toxicity and/or failure occurred within the first 6 months (64%), with only 4 events beyond 2 years. Conclusion: HPV-associated oropharyngeal cancer treated with definitive RT has excellent outcomes. Of the few patients that suffered a local failure, all were identified with physical exam. Symptoms and/or 3-month posttreatment PET/CT identified 92% of locoregional failures and 71% of distant failures. Given these findings, if posttreatment of PET/CT is negative, no further imaging is warranted. Follow-up should include history and physical exam with direct visualization. Author Disclosure: J.M. Frakes: None. A.O. Naghavi: None. T. Strom: None. A.R. Giuliano: None. L.B. Harrison: None. A. Trotti: None. J.J. Caudell: None.

Predictors of Complete Response and Disease Recurrence Following Chemoradiation for Rectal Cancer.

Approximately 10-40% of rectal patients have a complete response (CR) to neoadjuvant chemoradiation (CRT), and these patients have improved survival. Thus, non-operative management ("watch-and-wait" approach) may be an option for select patients. We aimed to identify clinical predictors of CR following CRT. Patients treated with definitive CRT for T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal cancer from August 2004 to February 2015 were retrospectively reviewed. Most patients were treated with 50.4 Gy radiation and concurrent 5-fluoruracil or capecitabine. Patients were considered to have a CR if surgical pathology revealed ypT0N0M0 (operative management), or if they had no evidence of residual disease on clinical and radiographic assessment (non-operative management). Statistical analysis was carried out to determine predictors of CR and long-term outcomes. Complete records were available on 138 patients. The median follow-up was 24.5 months. Thirty-six patients (26.3%) achieved a CR; 30/123 operatively managed patients (24.5%) and 6/15 (40%) non-operatively managed patients. None of the 10 patients with mucinous adenocarcinoma achieved a CR. Carcinoembryonic antigen (CEA) ≥5 μg/L at diagnosis (OR 0.190, 95% CI 0.037-0.971, p = 0.046), tumor size ≥3 cm (OR 0.123, 95% CI 0.020-0.745, p = 0.023), distance of tumor from the anal verge ≥3 cm (OR 0.091, 95% CI 0.013-0.613, p = 0.014), clinically node-positive disease at diagnosis (OR 0.201, 95% CI 0.045-0.895, p = 0.035), and interval from CRT to surgery ≥8 weeks (OR 5.267, 95% CI 1.068-25.961, p = 0.041) were independent predictors of CR. The CR group had longer 3-year distant metastasis-free survival (DMFS) (93.7 vs. 63.7%, p = 0.016) and 3-year disease-free survival (DFS) (91.1 vs. 67.8%, p = 0.038). Three-year locoregional control (LRC) (96.6 vs. 81.3%, p = 0.103) and overall survival (97.2 vs. 87.5%, p = 0.125) were higher in the CR group but this did not achieve statistical significance. CR was not an independent predictor of LRC, DMFS, or DFS. CEA at diagnosis, tumor size, tumor distance from the anal verge, node positivity at diagnosis, and interval from CRT to surgery were predictors of CR. These clinical variables may offer insight into patient selection and timing of treatment response evaluation in the watch-and-wait approach.

Toxicity and efficacy of accelerated radiotherapy with concurrent weekly cisplatin for locally advanced head and neck carcinoma.

The purpose of this report was to present the results of accelerated radiotherapy (RT) with concomitant weekly cisplatin in head and neck cancer. One hundred six patients received concomitant cisplatin 40 mg/m(2) weekly with accelerated RT up to a dose of 68 Gy over 5.5 weeks. Ninety-nine percent of the patients received planned RT and 90% received ≥5 cycles of cisplatin. Moist desquamation of skin developed in 45% and confluent mucositis in 82%. Feeding tubes were required in 79% of the patients, and after 12 months in 4%. One patient developed nephrotoxicity. Three-year locoregional control, disease-free survival (DFS), and overall survival (OS) were 72%, 54%, and 61%, respectively. Human papillomavirus (HPV) status was positive on polymerase chain reaction (PCR) and p16 in 11 of 50 patients with oropharyngeal carcinoma. Three-year OS was 81% and 66% in HPV-positive versus HPV-negative patients with oropharyngeal carcinoma. Concomitant weekly cisplatin 40 mg/m(2) with accelerated RT was well tolerated and treatment compliance was high. © 2015 Wiley Periodicals, Inc. Head Neck 38: E559-E565, 2016.

Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and laryngeal squamous cell carcinoma: mature treatment results and patterns of locoregional failure.

PurposeTo assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.MethodsData from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities. Time-to-event endpoints were estimated using Kaplan-Meier method, and univariate and multivariate analyses were performed using Cox proportional hazards models. Recurrent gross tumor volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20–95% inside CTV; out-volume, < 20% inside CTV).ResultsFifty patients (stage III: 14, IVa: 33, IVb: 3) completed treatment and were included in the analysis (median follow-up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96% and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%, respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We identified 10 patients with LRF (8 local, 1 regional, 1 local + regional). Six out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4 RTVs were marginal to the high-dose CTVs.ConclusionThe treatment of locally advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of LRFs in relation to CTVs showed in-volume relapses to be the major mode of recurrence indicating that novel strategies to overcome radioresistance are required.

Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option.

Background:Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for patients with rectal cancer receiving chemoradiotherapy. Its place in the treatment of locally advanced anal carcinoma (AC), however, remains undetermined. We investigated whether capecitabine is as effective as 5-FU in the treatment of patients with locally advanced AC.Methods:One hundred and five patients with squamous cell AC stage T2-4 (T2>4 cm), N0-1, M0 or T1-4, N2-3, M0, were included in this retrospective study. Forty-seven patients were treated with continuous 5-FU (750 mg m−2) on days 1–5 and 29–33, mitomycin C (MMC, 10 mg m−2) on day 1, and radiotherapy; 58 patients were treated with capecitabine (825 mg m−2 b.i.d. on weekdays), MMC (10 mg m−2) on day 1, and radiotherapy. The primary end points of the study were: clinical complete response rate, locoregional control (LRC) and overall survival (OS). Secondary end points were: colostomy-free survival (CFS), toxicity and associations of genetic polymorphisms (GSTT1, GSTM1, GSTP1 and TYMS) with outcome and toxicity.Results:Clinical complete response was achieved in 41/46 patients (89.1%) with 5-FU and in 52/58 patients (89.7%) with capecitabine. Three-year LRC was 76% and 79% (P=0.690, log-rank test), 3-year OS was 78% and 86% (P=0.364, log-rank test) and CFS was 65% and 79% (P=0.115, log-rank test) for 5-FU and capecitabine, respectively. GSTT1 and TYMS genotypes were associated with severe (grade 3–4) toxicity.Conclusions:Capecitabine combined with MMC and radiotherapy was equally effective as 5-FU-based chemoradiotherapy. This study shows that capecitabine can be used as an acceptable alternative to 5-FU for the treatment of AC.

GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy

BackgroundOral cavity cancers (ORC) are the most common cancers, and standard treatment is radical surgery with postoperative radiotherapy. However, locoregional failure remains a major problem, indicating radioresistance an important issue. Our previous work has shown that GP96 contributed to radioresistance in nasopharyngeal and oral cancer cell lines. In this study, we determined clinical significance of GP96 in ORC by evaluation of GP96 expression and its association with disease prognosis in patients receiving radiotherapyMethodsTotal of 79 ORC patients (77 males, median age: 48 years old) receiving radical surgery and postoperative radiotherapy between Oct 1999 and Dec 2004 were enrolled. Patients in pathological stages II, III and IV were 16.5%, 16.5% and 67%, respectively. For each patient, a pair of carcinoma tissue and grossly adjacent normal mucosa was obtained. GP96-expression was examined by western blot analysis, and the association with clinicopathological status was determined.ResultsThree-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) rates were 69%, 79%, 63% and 57%, respectively. We found that 55 patients (70%) displayed GP96-overexpression in the tumor tissue, which correlated with a higher pN stage (p = 0.020) and tumor depth (> 10 mm) (p = 0.045). Nodal extracapsular spreading (ECS) and GP96-overexpression predicted adverse LRC (p = 0.049 and p = 0.008). When stratified by nodal ECS, the adverse impact of GP96 remained significant in three-year LRC (p = 0.004). In multivariate analysis, GP96-overexpression was also an independent predictor of LRC, DSS and OS (p = 0.018, p = 0.011 and p = 0.012).ConclusionGP96 may play roles in radioresistance which attributes to tumor invasiveness in oral cancer patients receiving radiotherapy. GP96 may serve as a novel prognostic marker of radiotherapy. However, further independent studies are required to validate our findings in a larger series.

Voice, swallowing and quality of life in patients after transoral laser surgery for supraglottic carcinoma

Transoral laser surgery is a conservative surgical method used to treat supraglottic carcinomas, but little is known about functional and quality of life (QOL) outcomes relative to extent of resection. We prospectively examined functional and oncological outcomes of 21 patients with T1-T3 supraglottic carcinomas underwent partial (group A, n = 8) or radical (group B, n = 13) laser supraglottic resection and bilateral neck dissection. Subjective and objective evaluation of voice, swallowing and QOL before and after endoscopic supraglottic resection were compared between the two groups. No major complications were encountered, but local recurrence developed in two patients (9%). Vocal function was not generally affected by surgery. Postsurgical swallowing and social eating scores were higher in group B than in group A (P < 0.05). Aspiration occurred in most patients soon after surgery, but recovered within 3-6 months, with recovery being faster in group A. Three-year locoregional control, disease-free survival and overall survival rates were 81%, 71% and 79%, respectively. Swallowing was affected by the extent of laser resection for supraglottic carcinomas, but eventually recovered in most patients, indicating favourable functional and oncological outcomes.

Concurrent, cisplatin-based chemotherapy with accelerated radiotherapy for advanced head and neck cancer patients

17019 Background As the altered fractionation has become a standard radiation treatment (RT) for moderately advanced head and neck cancer (H&NC) patients, we decided to make use the accelerated fractionation with systemic cisplatin-based therapy for highly advanced lesions. Methods Fifty eight patients with H&NC in clinical stage IV treated between 1999 and 2003 were prospectively evaluated. Treatment assumed the administration of 3 courses of cisplatin (100mg/m2) and vinorelbin, and continuously fractionated irradiation (7 fractions per week) to the total dose of 68Gy in 40 fractions. Results One patient death could be related to the treatment. Planned RT dose has been realized in 56 patients (96%) but in 11 patients total dose was escalated within the range 70–78Gy because of residual lesion investigated at the end of treatment. Between 15th and 48th day of combined treatment all patients developed confluent mucositis, which lasted about 60 days (median value). All required anti-inflammatory and analgesic treatment including corticosteroids and opioids respectively. Tube feeding was realized in 15% of pts. During the first year of the study all 16 consecutive patients have been developing grade 3–4 neutropenia and 31% of them grade 3–4 anaemia. This was the reason to give only 2 courses of chemotherapy for 12 of them (75%) and to modify the schedule with drug-dose reduction: by 25% the dose of cisplatin and by 33% the dose of vinorelbin. Generally all patients received at least 2 courses of chemotherapy and 44of them (76%) realized full prescribed chemotherapy regimen (in 28 pts chemotherapy was widened up to 4 courses). Median follow-up is 35 months. Three-year loco-regional control and disease free survival rates are respectively 60% and 50%. During follow-up 15 patients died - 12 of them from cancer disease, in 9 patients salvage surgery was performed: 6 lymph node resections and 3 resections of residual tumour. Organ preservation has been noted at 65% of patients. Conclusions Concomitant chemo-radiotherapy in patients with advanced, fairly unresectable head and neck tumours produces very promising early results. After chemotherapy dose reduction the treatment is feasible in clinical practice and bow us towards a multicenter phase III study. No significant financial relationships to disclose.

A Phase II Multi-institutional Trial of Chemoradiation Using Weekly Docetaxel and Erythropoietin for High-Risk Postoperative Head and Neck Cancer Patients

To determine efficacy and toxicities of postoperative concurrent chemoradiation using docetaxel in high-risk head and neck cancer. High-risk patients were enrolled 2-8 weeks after surgery. Treatment included 60 Gy for 6 weeks with weekly docetaxel 25 mg/m(2) and erythropoietin alpha 40,000 U for hemoglobin < or =12 g/dL. Primary endpoints included locoregional control (LC), disease-free survival (DFS), and patterns of failure (POF). Secondary endpoints were toxicity and quality of life. Eighteen patients were enrolled (14 male, 4 female), aged 24-70 years (median, 55 years). Primary site included oropharynx = 7, oral cavity = 8, hypopharynx = 1, and larynx = 2. Pathologic American Joint Committee on Cancer Stage was III = 3 patients, IV = 15 patients. High-risk eligibility included > or =2 positive lymph nodes = 13, extracapsular extension = 10, positive margins = 8 (11 patients with two or more risk factors). Docetaxel was reduced to 20 mg/m(2)/week after 5 patients had prolonged Grade 3 or higher mucositis. Overall, number of doses delivered was 2 of 6 = 1, 3 of 6 = 2, 4 of 6 = 2, 5 of 6 = 4, 6 of 6 = 9 patients. With median follow-up of 30 months (range, 5-66), 10 (56%) patients are alive and have no evidence of disease (NED); POF: three local recurrences (two with distant) and 1 distant only. One-year survival was 76%, median PFS and DFS had not been reached. Three-year LC was 82%. No Grade 3 or higher late toxicities were observed, although a few cases of prolonged mucositis and taste loss (>3 months) were seen, particularly at 25 mg/m(2)/week. Postoperative radiation therapy with weekly docetaxel 20 or 25 mg/m(2)/week for high-risk postoperative head and neck cancer caused intolerable mucosal toxicity, prompting early study termination. Further studies should consider 15 mg/m(2). Actuarial 3-year LC is 82%, similar to cisplatin-based chemoradiation regimens. Distant metastasis remains an important issue requiring additional systemic interventions.