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Comparison of clinical and pathological staging in head and neck squamous cell carcinoma: results from Intergroup Study ECOG 4393/RTOG 9614.

ABSTRACT: To compare the results of clinical and pathological staging for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) and to examine patterns and ramifications of the disparity between staging methods.Prospective inception cohort (median follow-up, 7 years).Multi-institutional cooperative group study (Eastern Cooperative Oncology Group 4393/Radiation Therapy Oncology Group 9614) involving 17 academic medical centers.A total of 560 patients with new-onset or recurrent HNSCC enrolled during a 7-year period.Surgical resection with curative intent with or without adjuvant or previous radiotherapy or chemotherapy.Clinical staging and pathological staging and the component TN tumor categories were compared with overall and disease-specific survival. Association of survival with staging was derived by means of the proportional hazards model.Of the 501 cases in which both clinical and pathological staging was available, a disparity was found between at least 1 component tumor category assigned by the 2 methods in almost 50% of cases. Both methods showed a strong association of stage with overall survival for the cohort at large. However, pathological nodal category was a superior predictor (P < .001 vs P = .005), whereas there was an advantage to pathological tumor category in predicting disease-specific survival (P = .01).Both staging methods are useful in predicting survival, whereas information gained at neck dissection regarding nodal metastases provides some refinement in prognostic results. These findings demonstrate the need for enhanced methods of tumor assessment and apparent benefit of data gathered at neck dissection for accurate disease assessment and stratification.

SUBMITTER: Koch WM

PROVIDER: S-EPMC2846171 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Comparison of clinical and pathological staging in head and neck squamous cell carcinoma: results from Intergroup Study ECOG 4393/RTOG 9614.

Koch Wayne M WM Ridge John A JA Forastiere Arlene A Manola Judith J

Archives of otolaryngology--head & neck surgery 20090901 9

<h4>Objectives</h4>To compare the results of clinical and pathological staging for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) and to examine patterns and ramifications of the disparity between staging methods.<h4>Design</h4>Prospective inception cohort (median follow-up, 7 years).<h4>Setting</h4>Multi-institutional cooperative group study (Eastern Cooperative Oncology Group 4393/Radiation Therapy Oncology Group 9614) involving 17 academic medical centers.<h4>Pa ...[more]

PMID: 19770416

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Project description:Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior to definitive surgical resection and would enhance pathological response compared with historical cohorts of patients with locoregionally advanced HNSCC treated with checkpoint inhibitor alone. The Neoadjuvant Immuno-Radiotherapy Trial was an investigator-initiated single institution phase Ib clinical trial that enrolled patients with previously untreated locally advanced HPV-positive and HPV-negative HNSCC between 2018 and 2019. Eligible patients were treated with neoadjuvant SBRT at a total dose of either 40 Gy in 5 fractions or 24 Gy in 3 fractions, delivered in a 1-week timespan, with or without nivolumab, prior to definitive surgical resection. Patients were then planned for treatment with adjuvant nivolumab for 3 months. The primary safety endpoint was unplanned delay in surgery considered to be at least possibly related to neoadjuvant treatment. The primary efficacy endpoints included pathological complete response (pCR), major pathological response (mPR), and the rate of clinical to pathological downstaging after neoadjuvant treatment. Twenty-one patients underwent neoadjuvant treatment, which was well tolerated and did not delay surgery, thus meeting the primary endpoint. Tissue responses were characterized by robust inflammatory infiltrates in the regression bed, plasma cells and cholesterol clefts. Among the entire study group, the mPR and pCR rate was 86% and 67%, respectively. Clinical to pathological downstaging occurred in 90% of the patients treated. These data demonstrate that radiation delivered only to the gross tumor volume combined with immunotherapy was safe, resulted in a high rate of mPR and should be further evaluated as a locally focused neoadjuvant therapy for patients with head and neck cancer. This study is registered with clinicaltrials.gov (NCT03247712) and is active, but closed to patient accrual.

Project description:Accurately identifying close or positive margins in real-time permits re-excision during surgical procedures. Intraoperative assessment of margins via gross examination and frozen section is a widely used tool to assist the surgeon in achieving complete resection. While this methodology permits diagnosis of freshly resected tissue, the process is fraught with misinterpretation and sampling errors. During fluorescence-guided surgery, an exogenous fluorescent agent specific for the target disease is imaged in order to navigate the surgical excision. As this technique quickly advances into the clinic, we hypothesize that the disease-specific fluorescence inherently contained within the resected tissues can be used to guide histopathological assessment. To evaluate the feasibility of fluorescence-guided pathology, we evaluated head and neck squamous cell carcinoma tumour specimens and margins resected from animals and patients after systemic injection of cetuximab-IRDye800CW. In a preclinical model of luciferase-positive tumour resection using bioluminescence as the gold standard, fluorescence assessment determined by closed-field fluorescence imaging of fresh resected margins accurately predicted the presence of disease in 33/39 positive margins yielding an overall sensitivity of 85%, specificity of 95%, positive predictive value (PPV) of 94%, and a negative predictive value (NPV) of 87%, which was superior to both surgical assessment (54%, 61%, 57%, and 58%) and pathological assessment (49%, 95%, 91%, and 66%), respectively. When the power of the technique was evaluated using human-derived tumour tissues, as little as 0.5mg (1mm(3)) of tumour tissue was identified (tumour-to-background-ratio:5.2). When the sensitivity/specificity of fluorescence-guided pathology was determined using traditional histological assessment as the gold standard in human tissues obtained during fluorescence-guided surgery, the technique was highly accurate with a sensitivity of 91%, specificity of 85%, PPV of 81%, and NPV of 93% for 90 human-derived samples. This approach can be used as a companion to the pathologist, eliminating confounding factors while impacting surgical intervention and patient management.

Project description:BackgroundTumorigenesis is a complex process of accumulated alteration in function of multiple genes and pathways. Wnt signalling pathway is involved in various differentiation events during embryonic development and is conserved in various species.ObjectiveA multicentre collaborative initiative is undertaken to study the occurrence, prognosis and molecular mechanism of HNSCC (Head and Neck Squamous Cell Carcinoma) which is highly prevalent in eastern parts of India. From a large cohort of HNSCC tissue repository, 67 cases were selected for multi-parametric investigation.Results67 cases showed stable ?-catenin expression. We have seen correlation, if any, of the transcription factor - ?-catenin, telomere maintenance and shelterin complex proteins - TRF2, Rap1 and hTert with respect to tumor differentiation and telomere dysfunction. Immunohistochemistry of ?-catenin protein showed stable and high expression in tumor when compared to stroma. MDSCC (Moderately Differentiated Squamous cell carcinoma) cases expressed nuclear expression of ?-catenin in invasive fronts and showed increased genomic instability. Higher frequency of Anaphase bridges was observed ranging from <3% in normal cut margin to 13% in WDSCC (Well differentiated squamous cell carcinoma) and 18% in MDSCC (Moderately differentiated Squamous cell carcinoma). There was significant decrease in telomere length in MDSCC (<4) when compared to the normal cut margin samples (<7). Quantitative Real Time-PCR confirmed a significant correlationship between stable ?-catenin expression and poor clinical and pathological outcome.ConclusionThe Stabilisation and accumulation of ?-catenin was significant and correlated well with de-differentiation process as well as prognosis and therapy outcome of the patients in the cohort. Expression status of molecular markers such as ?-catenin, hTert, TRF2 and RAP1 correlate significantly with the process of tumorigenesis and prognosis and may play a role in therapeutic management of Head and neck patients.

Project description:PurposeTo report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with high-risk pathologic features.Patients and methodsEligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases. Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m(2) or docetaxel 15 mg/m(2) once per week.ResultsBetween April 2004 and December 2006, 238 patients were enrolled. With a median follow-up of 4.4 years, 2-year overall survival (OS) was 69% for the cisplatin arm and 79% for the docetaxel arm; 2-year disease-free survival (DFS) was 57% and 66%, respectively. Patients with p16-positive oropharynx tumors showed markedly improved survival outcome relative to patients with p16-negative oropharynx tumors. Grade 3 to 4 myelosuppression was observed in 28% of patients in the cisplatin arm and 14% in the docetaxel arm; mucositis was observed in 56% and 54%, respectively. DFS in this study was compared with that in the chemoradiotherapy arm of the RTOG-9501 trial (Phase III Intergroup Trial of Surgery Followed by Radiotherapy Versus Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck), which had a hazard ratio of 0.76 for the cisplatin arm versus control (P = .05) and 0.69 for the docetaxel arm versus control (P = .01), reflecting absolute improvement in 2-year DFS of 2.5% and 11.1%, respectively.ConclusionThe delivery of postoperative chemoradiotherapy and cetuximab to patients with SCCHN is feasible and tolerated with predictable toxicity. The docetaxel regimen shows favorable outcome with improved DFS and OS relative to historical controls and has commenced formal testing in a phase II/III trial.

Project description:Importance:Previous studies have shown that the AJCC Cancer Staging Manual, 7th edition (AJCC 7), tumor classification for cutaneous squamous cell carcinoma (CSCC) failed to accurately stratify disease-related outcomes. The recently released 8th edition (AJCC 8) features a revised tumor classification for only head and neck CSCC (HNCSCC). Objective:To compare AJCC 7 and AJCC 8 tumor classifications for HNCSCC and to validate AJCC 8. Design, Setting, and Participants:This was a 10-year retrospective cohort study (2000-2009) at an academic tertiary care center reviewing 680 primary HNCSCC tumors in 459 patients. Main Outcomes and Measures:Primary HNCSCC tumors were reviewed for disease-related outcomes (DROs): local recurrence (LR), nodal metastasis (NM), and disease-specific death (DSD). Tumors were stratified by AJCC 7 and AJCC 8 tumor classification. Distinctiveness (outcome differences between categories), homogeneity (outcome similarity within categories), and monotonicity (outcome worsening with increasing categories) were assessed for both classifications. Results:Most of the 459 patients were white (451 [98.3%]) and male (312 [68.0%]). AJCC 8 high tumor categories (T3/T4) accounted for 121 (17.8%) of total cases but 50 of 71 DROs (70.4%) (22 of 34 of LRs [64.7%], 17 of 24 NMs [70.8%], and 11 of 13 of DSDs [84.6%]). This was a significant improvement over AJCC 7, where only 12 of 71 DROs (16.9%) (4 of 34 LRs [11.8%], 3 of 24 NMs [12.5%], and 5 of 13 DSDs [38.5%]) occurred in T3/T4 categories. However, AJCC 8 T2 and T3 were indistinct, with overlapping 95% CIs for 10-year cumulative incidences of LR, NM, and DSD. The 10-year cumulative incidence of DROs in the 119 AJCC 8 T3 cases were 19.7% (95% CI, 13.0%-29.7%) for LR, 14.1% (95% CI, 9.7%-20.7%) for NM, and 9.3% (95% CI, 6.8%-14.0% for DSD). Conclusions and Relevance:AJCC 8 demonstrates superior homogeneity and monotonicity compared with AJCC 7. It now may be possible for AJCC 8 HNCSCC T2, T3, and T4 cases to be recorded and tracked by tumor registries because they represented a 23.1% subset in this study, which includes nearly all poor outcomes (85.9%). Further work is needed to validate AJCC 8 with population-level data and to compare AJCC 8 performance against alternative tumor classifications.

Dataset Information

Comparison of clinical and pathological staging in head and neck squamous cell carcinoma: results from Intergroup Study ECOG 4393/RTOG 9614.

Publications

Comparison of clinical and pathological staging in head and neck squamous cell carcinoma: results from Intergroup Study ECOG 4393/RTOG 9614.

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