Tumor stage, human papillomavirus and smoking status affect the survival of patients with oropharyngeal cancer: an Italian validation study

Granata, Roberta; Miceli, Rosalba; Orlandi, Ester; Perrone, Francesco; Cortelazzi, Barbara; Franceschini, Marzia; Locati, Laura D.; Bossi, Paolo; Bergamini, Cristiana; Mirabile, Aurora; Mariani, Luigi; Olmi, Patrizia; Scaramellini, G.; Potepan, Paolo; Quattrone, Pasquale; Ang, K. Kian; Licitra, Lisa

doi:10.1093/annonc/mdr544

Cited by 92 publications

(79 citation statements)

References 21 publications

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“…The importance of an upfront TURBT in achieving optimal results has been previously reported (2). The prognostic impact of the number of pack years and smoking during the period of irradiation has also already been demonstrated for other tumours such as lung and headand-neck cancer (12)(13)(14)(15). The fact that the findings of the present study agree with the results of previous studies demonstrates consistency of the data obtained from the present analyses.…”

Section: Discussionsupporting

confidence: 90%

Factors Impacting the Overall Survival of Patients Irradiated for Invasive Carcinoma of the Urinary Bladder

Rades

Manig

Schild

2017

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Abstract. Background A considerable number of patients with carcinoma of the urinary bladder are treated with an organ-preserving approach, mostly consisting of transurethral resection of the bladder tumour (TURBT) followed by irradiation with or without concurrent chemotherapy (1-3). Since many of these patients present with significant comorbidities, a personalised treatment program is often required. Such a program should ideally consider several patient-related factors, including the patient's social situation, patient treatment preference, additional diseases, general condition and remaining life-span. It has been reported for other situations of patients with carcinoma of the urinary bladder, such as metastatic or recurrent disease, that those patients with a poor survival prognosis should receive shorter-course and less aggressive treatments, since low treatment-related toxicity not impairing the patient's quality of life is very important for this group (4-7). Those patients with a much better prognosis should benefit from more aggressive longer-course treatments including systemic therapies leading to better control of the malignant disease and significant prolongation of the patient's survival time.In order to tailor the treatment regimen to the patient's individual situation, the ability to estimate their survival time is desirable. This goal could be achieved with a clear understanding of the independent predictors of survival identified specifically for patients with carcinoma of the urinary bladder. This study aimed to identify such predictors in a cohort of patients who received organ-preserving treatment including local irradiation. Patients and MethodsThis retrospective study included 61 patients treated with definitive irradiation for carcinoma of the urinary bladder cancer. Irradiation was performed as computed tomography-based conformal radiotherapy with 6-18 MV photons. The median dose was 59.4 Gy (range=50.4 to 63.0 Gy), which was delivered with conventional fractionation of 1.8 to 2.0 Gy on five consecutive days per week. In two-thirds of the patients (N=40), the total dose was 59.4 Gy given with 1.8 Gy per fraction. In 45 patients, irradiation was supplemented with simultaneous chemotherapy, which was mainly cisplatin-or carboplatin-based (N=27). The characteristics of the 61 patients are summarized in Table I. For the 61 patients, a total of 11 potential predictive factors were analysed with respect to an association with overall survival. These factors were gender, age (≤77 vs. >77 years; median age=77 years), T-stage (T1-2 vs. T>2a vs. T3-4), N-stage (N0 vs. N1/2), histological grading (G2 vs. G3), pack years smoked prior to irradiation (<40 vs. ≥40 years), smoking during irradiation (no vs. yes), transurethral resection of the bladder tumour prior to irradiation (TURBT; no vs. 741

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Section: Discussionsupporting

confidence: 90%

Factors Impacting the Overall Survival of Patients Irradiated for Invasive Carcinoma of the Urinary Bladder

Rades

Manig

Schild

2017

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“…For p16 expression in oropharyngeal SCC, virtually every study has shown strong differences in overall, disease-free, recurrence-free, and disease-specific survival, depending on the respective outcome measures provided in the particular study [2, 3, 5-7, 9, 12, 19]. This has been independent of treatment modality, either primary chemoradiation, induction chemotherapy followed by definitive radiotherapy, or primary surgery with or without postoperative chemo radiotherapy [2,5,9,12,19,20]. Hazard ratios for overall, progressionfree, disease-free, and disease-specific survival for p16 positive versus negative cases are consistently low (Table 2) [2,3,5,6,12,21].…”

Section: Introductionmentioning

confidence: 99%

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

Lewis

2012

Head and Neck Pathol

203

197

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It is widely acknowledged that human papillomavirus (HPV)-related oropharyngeal carcinoma is a biologically unique form of head and neck cancer that should be singled out and treated differently. It is now incumbent to find a test (or combination of tests) that accurately identifies cancers with the associated favorable prognosis for proper patient counseling and management and for placing patients in the correct treatment arms in the emerging clinical trials that are attempting to establish unique treatment types and approaches. The test (or combination of tests) that are utilized must be widely available, reliable, easy to interpret, and wellvalidated. While HPV-specific testing seems completely logical to use as a single test or one of a combination of tests, it turns out to be quite complicated in practice. Because of the different forms of the virus, the differing types of HPV-specific tests can give different information. HPV DNA, RNA, and protein assays have varying sensitivities for virus detection and also varying availability from formalin-fixed, paraffin-embedded tissue. Since p16 protein over expression is very sensitive for the presence of transcriptionally-active HPV and since it correlates strongly with patient outcomes, is widely available, and easy to interpret, it appears to currently be the single test that combines all of the desired attributes in a risk stratification marker for widespread implementation in clinical and research study settings. This article will review the literature on p16 immunohistochemistry and its relation to HPV-specific testing, discuss some practical issues related to its implementation, and present the case for why it should be the single test used for this purpose.

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“…Furthermore, the results of the previously mentioned studies and meta-analyses might have been infl uenced by the patients' smoking habit, as smoking during radiotherapy has been shown to impair tumour oxygenation. Th is has been shown in particular for non-small cell lung cancer and headand-neck cancer [7,[22][23][24]. In a retrospective study of 181 patients with non-small cell lung cancer, loco-regional control at 2 years was better in patients who did not smoke than in patients who did smoke during radiotherapy (58% vs. 41%, p < 0.001) [7].…”

Section: Erythropoietin Stimulating Agents (Esas)mentioning

confidence: 98%

Challenges of anemia correction during radiotherapy and chemoradiation

Rades

Schild

2012

memo

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Th e eff ect of radiotherapy depends on optimal tumour oxygenation, as tumour hypoxia impairs the production of radiation-induced cytotoxic free radicals resulting in less tumour cell kill. Th e range of haemoglobin levels optimal for tumour oxygenation is 12-14 g/dl in women and 13-15 g/dl in men. It appears reasonable to elevate the haemoglobin level in anaemic cancer patients into this optimal range. Th is may be achieved with red blood cell transfusions (RBCT) or erythropoiesis stimulating agents (ESAs). However, RBCT have had negligible or even negative eff ect on patient outcome, possibly because RBCT induce immunosuppression or result in haemoglobin levels too high for optimal tumour oxygenation. Several randomized trials have demonstrated that patients irradiated for head-and-neck cancer had worse outcomes with ESAs than the control group. However, in the majority of these trials, over-treatment with ESAs resulted in haemoglobin levels above the optimal range. Tumour oxygenation is impaired by inappropriately high haemoglobin levels due to increased blood viscosity and decreased tumour cell perfusion. Th is concept is supported by the fi ndings of prospective studies in cervix cancer and esophageal cancer patients. In these studies the ESA administration was withheld at a haemoglobin level of 14 g/dl resulting in a positive eff ect of ESAs on treatment outcome. In summary, the eff ect of RBCT and particularly of ESAs during radiotherapy remains unclear. Further randomized trials are required. Until such trials are available, one should follow the ASCO and ESMO guidelines that are very conservative regarding the administration of ESAs during radiotherapy and chemoradiation.

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Tumor stage, human papillomavirus and smoking status affect the survival of patients with oropharyngeal cancer: an Italian validation study

Abstract: This study validates the risk grouping previously identified. Risk-driven clinical decision making and trial designs will help in better defining the most appropriate treatment in OPC patients.

Cited by 92 publications

References 21 publications

Factors Impacting the Overall Survival of Patients Irradiated for Invasive Carcinoma of the Urinary Bladder

Factors Impacting the Overall Survival of Patients Irradiated for Invasive Carcinoma of the Urinary Bladder

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

Challenges of anemia correction during radiotherapy and chemoradiation

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