Dataset Information

Age-adjusted comorbidity and survival in locally advanced laryngeal cancer.

ABSTRACT: BACKGROUND:The purpose of this study was to quantify the relationship among age, pretreatment comorbidity, and survival outcomes in patients with locally advanced laryngeal cancer. METHODS:Baseline comorbidity data were collected and age-adjusted Charlson Comorbidity Index (CCI) was calculated for each case. Kaplan-Meier and Cox proportional hazards modeling were used to determine associations with survival. RESULTS:For 548 patients, with a median age of 59 years (range 31-91 years), 58% were treated with larynx preservation and the rest with total laryngectomy and adjuvant radiotherapy (RT). Two hundred thirty-eight patients (43%) had at least 1 comorbidity each. Cardiovascular diseases were the most common comorbidities (19%). The 5-year overall survival (OS) for patients with CCI ?3 (n = 442) were superior to CCI >3 (n = 106; 60% vs 41%; P < .0001), although the 5-year disease-specific survival (DSS) rates were not significantly different. The 5-year noncancer CSS was better for age-adjusted CCI ?3 (88% vs 67%; P < .0001). CONCLUSION:The age-adjusted CCI is a significant predictor of noncancer CSS and OS for patients with locally advanced laryngeal cancer but is not associated with DSS.

SUBMITTER: Multidisciplinary Larynx Cancer Working Group

PROVIDER: S-EPMC6131035 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Age-adjusted comorbidity and survival in locally advanced laryngeal cancer.

Mulcahy Collin F CF Mohamed Abdallah S R ASR Kanwar Aasheesh A Hutcheson Katherine A KA Ghosh Alokananda A Vock David D Weber Randal S RS Lai Stephen Y SY Gunn Gary Brandon GB Zafereo Mark M Morrison William H WH Ferrarotto Renata R Garden Adam S AS Rosenthal David I DI Fuller Clifton D CD

Head & neck 20180513 9

<h4>Background</h4>The purpose of this study was to quantify the relationship among age, pretreatment comorbidity, and survival outcomes in patients with locally advanced laryngeal cancer.<h4>Methods</h4>Baseline comorbidity data were collected and age-adjusted Charlson Comorbidity Index (CCI) was calculated for each case. Kaplan-Meier and Cox proportional hazards modeling were used to determine associations with survival.<h4>Results</h4>For 548 patients, with a median age of 59 years (range 31- ...[more]

PMID: 29756307

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Project description:For long, the treatment of locoregionally advanced laryngeal and hypopharyngeal squamous cell cancers (SCC) consisted of either total laryngectomy (TL) or definitive radiotherapy (RT). The development of induction cisplatin plus 5-fluorouracil (PF) and the correlation between chemosensitivity and radiosensitivity in previously untreated patients opened a new era of treatment aiming at laryngeal preservation (LP). The fundamental concept was to employ induction PF in order to select patients for subsequent treatment with either TL or RT according to tumor response to PF. The first two trials (VALGSG for laryngeal SCC and EORTC 24891 for hypopharyngeal SCC) concluded that such an approach could preserve nearly 60% of larynx without deleterious impact on survival. The EORTC 24954 trial compared 4 cycles of induction PF followed by RT in good responders vs. alternating PF-RT in laryngeal and hypopharyngeal SCC. There was no significant difference in 5-year overall survival with a functional larynx between the two arms (31 vs. 35%). The GORTEC 2000-01 trial compared induction PF to induction PF plus docetaxel (TPF) both followed by RT in good responders in larynx and hypopharynx SCC. The 5-year LP was significantly higher in the TPF arm (60 vs. 39%) but without a difference in survival. The RTOG 91-11 trial compared induction PF followed by RT in good responders vs. concurrent chemoradiotherapy (chemo-RT) vs. RT alone in laryngeal SCC. There was no significant difference in 5-year laryngectomy-free survival between the patients treated with induction chemotherapy (44%) vs. those treated with chemo-RT (47%), both being superior to RT alone (34%). At 5 years, LP was superior with chemo-RT: 84 vs. 71% with induction PF. Two phase II trials explored the role of cetuximab (E) in LP in laryngeal and hypopharyngeal SCC. The TREMPLIN trial compared RT+E or chemo-RT (RT + P) after TPF. The DeLOS-II trial compared TPE followed by RT+E vs. TP followed by RT. However, these trials failed to indicate an advantage for the incorporation of E in the treatment paradigm. To date, two approaches for LP have been validated: induction TPF followed by RT for laryngeal and hypopharyngeal SCC and concurrent chemo-RT for laryngeal SCC. An ongoing trial (SALTORL) is comparing these two approaches, induction TPF and chemo-RT, in laryngeal/ hypopharyngeal SCC.

Project description:BackgroundParathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients.MethodsWe conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab.ResultsThe expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029).ConclusionsIn LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.

Project description:ImportanceUse of chemoradiotherapy for advanced laryngeal cancer led to a major shift in treatment as an alternative to laryngectomy. Despite widespread adoption of chemoradiotherapy, survival rates have not improved and the original premise of matching neoadjuvant chemotherapy tumor response to determine subsequent treatment has not been followed.ObjectiveTo determine whether improved survival could be achieved by incorporating a single cycle of neoadjuvant chemotherapy to select patients with advanced disease for either laryngectomy or concurrent chemoradiotherapy.Design, setting, and participantsAn unselected cohort of 247 patients with laryngeal cancer in an academic institution between 2002 and 2012 was evaluated. Patients with limited disease (stages I and II) underwent endoscopic resection, radiotherapy, or chemoradiotherapy for deeply invasive T2 lesions. For patients with advanced disease (stages III and IV), neoadjuvant chemotherapy, concurrent chemoradiotherapy, or primary surgery was recommended. Overall survival (OS) and disease-specific survival (DSS) were analyzed. Median follow-up was 48 months. The study was conducted from January 1, 2002, to December 31, 2012; data analysis was completed December 1, 2015.InterventionsEndoscopic resection, radiotherapy, chemoradiotherapy, neoadjuvant chemotherapy, concurrent chemoradiotherapy, and primary surgery.Main outcomes and measuresOverall survival and DSS.ResultsOf the 247 patients, 191 (77.3%) were male; mean (SD) age was 59.6 (10.4) years. Of 94 patients with limited disease, 33 (35.1%) underwent endoscopic resection; 50 (53.2%), radiotherapy alone; and 11 (11.7%), chemoradiotherapy for deeply invasive T2 lesions. Of 153 patients with advanced disease, 71 (46.4%) received neoadjuvant chemotherapy; 50 (32.7%), concurrent chemoradiotherapy; and 32 (20.9%), surgery. Five-year OS and DSS was 75% (95% CI, 68%-81%) and 83% (95% CI, 77%-88%), respectively, for the entire cohort. The DSS was 92% (95% CI, 83%-97%) for patients with stage I or II and 78% (95% CI, 69%-84%) for patients with stage III or IV disease. For patients with advanced disease, 5-year OS and DSS ranged from 78% (95% CI, 55%-90%) and 91% (95% CI, 67%-98%), respectively, for surgery; to 76% (95% CI, 63%-85%) and 79% (95% CI, 67%-88%), respectively, for neoadjuvant bioselection; and to 61% (95% CI, 44%-75%) and 66% (95% CI, 48%-79%), respectively, for primary chemoradiotherapy. Propensity-adjusted, multivariable controlling for known prognostic factors DSS was significantly improved in the neoadjuvant group compared with the chemoradiotherapy group (hazard ratio [HR], 0.48; 95% CI, 0.29-0.80).Conclusions and relevanceSuperior survival rates were achieved with a bioselective treatment approach using a single cycle of neoadjuvant chemotherapy. Good survival rates were also achieved in patients selected for primary surgery, and both neoadjuvant chemotherapy and primary surgery were better than survival rates with concurrent chemoradiotherapy, suggesting that the optimal individualized treatment approach for patients with advanced laryngeal cancer has not yet been defined.

Dataset Information

Age-adjusted comorbidity and survival in locally advanced laryngeal cancer.

Publications

Age-adjusted comorbidity and survival in locally advanced laryngeal cancer.

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