Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Strahlentherapie und Onkologie
Published in: Strahlentherapie und Onkologie 9/2022

Open Access 31-03-2022 | Original Article

Mutagen sensitivity and risk of second cancer in younger adults with head and neck squamous cell cancer: 15-year results

Authors: B. Bukovszky, DMD, J. Fodor, PhD DSc, G. Székely, S. Zs. Kocsis, PhD, F. Oberna, PhD, T. Major, PhD DSc, Z. Takácsi-Nagy, PhD, C. Polgár, PhD DSc, Z. Jurányi, PhD

Published in: Strahlentherapie und Onkologie | Issue 9/2022

Login to get access

Abstract

Purpose

To evaluate the mutagen sensitivity phenotype on the risk of second primary cancer (SPC) in patients with head and neck squamous cell carcinoma (HNSCC), and to estimate the long-term rate of SPC and the outcome with SPC.

Methods

A survey was made regarding SPC among 124 younger (≤ 50 years) adults with HNSCC who were enrolled in a pretreatment mutagen sensitivity investigation during 1996–2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantifying the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (> 1 b/c) or not hypersensitive (≤ 1 b/c).

Results

Mean follow-up time for all patients was 68 months (range: 5–288 months), and the 15-year cancer-specific survival was 15%. Twenty patients (16%) developed a SPC (15-year estimated rate: 41%), and half of them was hypersensitive. The crude rate of SPC for hypersensitive (n = 65) or not hypersensitive (n = 59) patients were 15 and 17%, respectively (p = 0.4272). The 15-year estimated rate of SPC for hypersensitive and not hypersensitive patients was 36 and 48%, respectively (p = 0.3743). Gender, UICC stages, anatomical sites of index cancer did not prove to be a significant risk factor for SPC. Forty-five percent of SPC developed after the 10-year follow-up. The 3‑year cancer-specific survival was 23% with SPC.

Conclusion

According to our findings, mutagen hypersensitivity was not associated with an increased SPC risk in HNSCC patients. Patients are at a lifelong risk of developing a SPC. Survival with SPC is very poor.
Literature
1.
Li FP, Montesano R (1994) Interactions of cancer susceptibility genes and environmental carcinogens. American Association for Cancer Research (AACR), International Agency for Research on Cancer (IARC) joint conference. Cancer Res 54:4243–4247PubMed
2.
Hsu TC, Spitz MR, Schantz SP (1991) Mutagen sensitivity: a biological marker of cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1:83–89PubMed
3.
Hsu TC (1983) Genetic instability in the human population: a working hypothesis. Hereditas 98:1–9CrossRef
4.
Spitz MR, Fueger JJ, Beddingfield NA, Annegers JF, Hsu TC, Newell GR, Schantz SP (1989) Chromosome sensitivity to bleomycin-induced mutagenesis, an independent risk factor for upper aerodigestive tract cancers. Cancer Res 49:4626–4628PubMed
5.
Spitz MR, Wu X, Jiang H, Hsu TC (1996) Mutagen sensitivity as a marker of cancer susceptibility. J Cell Biochem Suppl 25S:80–84CrossRef
6.
Lippman SM, Hong WK (1989) Second malignant tumors in head and neck squamous-cell carcinoma—the overshadowing threat for patients with early-stage disease. Int J Radiat Oncol Biol Phys 17:691–694CrossRef
7.
Schottenfeld D, Gantt RC, Wynder EL (1974) The role of alcohol and tobacco in multiple primary cancers of the upper digestive system, larynx, and lung: a prospective study. Prev Med 3:277–293CrossRef
8.
Silverman S, Gorsky M, Greenspan D (1983) Tobacco usage in patients with head and neck carcinomas: a follow-up study on habit changes and second primary oral/oropharyngeal cancers. J Am Dent Assoc 106:33–35CrossRef
9.
Day GL, Blot WJ, Shore RE, McLaughlin JK, Austin DF, Greenberg RS et al (1994) Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86:131–137CrossRef
10.
Khuri FR, Kim ES, Lee JJ, Winn RJ, Benner SE, Lippman SM et al (2001) The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial. Cancer Epidemiol Biomarkers Prev 10:823–829PubMed
11.
Do KA, Johnson MM, Lee JJ, Wu XF, Dong Q, Hong WK et al (2004) Longitudinal study of smoking patterns in relation to the development of smoking-related secondary primary tumors in patients with upper aerodigestive tract malignancies. Cancer 101:2837–2842CrossRef
12.
Schantz SP, Spitz MR, Hsu TC (1990) Mutagen sensitivity in patients with head and neck cancers: a biological marker for risk of multiple primary malignancies. J Natl Cancer Inst 82:1773–1775CrossRef
13.
Spitz MR, Hoque A, Trizna Z, Schantz SP, Amos CI, King TM et al (1994) Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract. J Natl Cancer Inst 86:1681–1684CrossRef
14.
Cloos J, Braakhuis BJM, Steen I, Copper MP, de Vries N, Nauta JJP, Snow GB (1994) Increased mutagen sensitivity in head-and-neck squamous-cell carcinoma patients, particularly those with multiple primary tumors. Int J Cancer 56:816–819CrossRef
15.
Székely G, Remenár E, Kásler M, Gundy S (2003) Does the bleomycin sensitivity assay express cancer phenotype? Mutagenesis 18:59–63CrossRef
16.
Székely G, Remenár E, Kásler M, Gundy S (2005) Mutagen sensitivity of patients with cancer at different sites of the head and neck. Mutagenesis 20:381–385CrossRef
17.
Kaplan E, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457–481CrossRef
18.
Cox DR (1972) Regression models and life-tables. J R Stat Soc Series B Stat Methodol 34:187–220
19.
Cloos J, Leemans CR, van der Sterre ML, Kuik DJ, Snow GB, Braakhuis BJ (2000) Mutagen sensitivity as a biomarker for second primary tumors after head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 9:713–717PubMed
20.
Minard CG, Spitz MR, Wu X, Hong WK, Etzel CJ (2006) Evaluation of glutathione S‑transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer. Cancer 106:2636–2644CrossRef
21.
Wu X, Gu J, Dong Q, Do KA, Hong WK, Spitz MR et al (2006) Joint effect of mutagen sensitivity and insulin-like growth factors in predicting the risk of developing secondary primary tumors and tumor recurrence in patients with head and neck cancer. Clin Cancer Res 12:7194–7201CrossRef
22.
Chuang SC, Scelo G, Tonita JM, Tamaro S, Jonasson JG, Kliewer EV et al (2008) Risk of second primary cancer among patients with head and neck cancers: a pooled analysis of 13 cancer registries. Int J Cancer 123:2390–2396CrossRef
23.
Rennemo E, Zätterström U, Boysen M (2008) Impact of second primary tumors on survival in head and neck cancer: an analysis of 2,063 cases. Laryngoscope 118:1350–1356CrossRef
24.
Tiwana MP, Hay J, Wu J, Wong F, Cheung W, Olson RA (2014) Incidence of second metachronous head and neck cancers: population-based outcomes over 25 years. Laryngoscope 124:2287–2291CrossRef
25.
Wolff HA, Wolff CRM, Hess CF, Jung K, Sennhenn-Kirchner S, Hinterthaner M et al (2013) Second primary malignancies in head and neck cancer patients: high prevalence of curable-stage disease. Strahlenther Onkol 189:874–880CrossRef
26.
Bugter O, van Iwaarden DLP, van Leeuwen N, Nieboer D, Dronkers EAC, Hardillo JAU et al (2021) A cause-specific Cox model for second primary tumors in patients with head and neck cancer: a RONCDOC study. Head Neck 43:1881–1889CrossRef
27.
Boakye EA, Buchanan P, Hinyard L, Osazuwa-Peters N, Simpson MC, Schootman M et al (2019) Trends in the risk and burden of second primary malignancy among survivors of smoking-related cancers in the United States. Int J Cancer 145:143–153CrossRef
28.
Arie GB, Shafat T, Belochitski O, El-Saied S, Joshua BZ (2021) Treatment modality and second primary tumors of the head and neck. Orl J Otorhinolaryngol Relat Spec 83:420–427CrossRef
29.
Adjei Boakye E, Buchanan P, Hinyard L, Osazuwa-Peters N, Schootman M, Piccirillo JF (2018) Incidence and risk of second primary malignant neoplasm after a first head and neck squamous cell carcinoma. JAMA Otolaryngol Head Neck Surg 144:727–738CrossRef
30.
Bhatia AK, Lee JW, Pinto HA, Jacobs CD, Limburg PJ, Rubin P et al (2017) Double-blind, randomized phase III trial of low-dose 13-cisretinoic acid in prevention of second primaries in head and neck cancer: long-term follow-up of a trial of the ECOG-ACRIN cancer research group (C0590). Cancer 123:4653–4662CrossRef
31.
Schwartz LH, Ozsahin M, Zhang GN, Touboul E, De Vataire F, Andolenko P et al (1994) Synchronous and metachronous head and neck carcinomas. Cancer 74:1933–1938CrossRef
32.
Adeel M, Siddiqi MI (2018) Metachronous second primary malignancy in head and neck cancer patients: Is five years of follow-up sufficient? J Korean Assoc Oral Maxillofac Surg 44:220–224CrossRef
Metadata
Title
Mutagen sensitivity and risk of second cancer in younger adults with head and neck squamous cell cancer: 15-year results
Authors
B. Bukovszky, DMD
J. Fodor, PhD DSc
G. Székely
S. Zs. Kocsis, PhD
F. Oberna, PhD
T. Major, PhD DSc
Z. Takácsi-Nagy, PhD
C. Polgár, PhD DSc
Z. Jurányi, PhD
Publication date
31-03-2022
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 9/2022
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-022-01917-2

Other articles of this Issue 9/2022

Strahlentherapie und Onkologie 9/2022 Go to the issue

Literatur kommentiert

Krebsprädispositions-Screening-Tools zur Vorhersage späterer maligner Erkrankungen bei Überlebenden nach einer Tumorerkrankung im Kindesalter

Original Article

Evaluating dosimetric parameters predictive of hematologic toxicity in cervical cancer patients undergoing definitive pelvic chemoradiotherapy

Original Article

Treatment outcomes of MRI-guided adaptive brachytherapy in patients with locally advanced cervical cancer: institutional experiences

Original Article

Isodoses—a set theory-based patient-specific QA measure to compare planned and delivered isodose distributions in photon radiotherapy

Original Article

Comparison of efficacy and safety between simultaneous integrated boost intensity-modulated radiotherapy and standard-dose intensity-modulated radiotherapy in locally advanced esophageal squamous cell carcinoma: a retrospective study

Original Article

Digital transfer in radiation oncology education for medical students—single-center data and systemic review of the literature