Risk Of Second Primary Tumors Research Articles

77 Emerging strategies for head & neck cancer prevention

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies mostly involving the oral cavity, oropharynx, hypopharynx, and larynx. All together they represent the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In this context, the risk of second primary tumors in the field of cancerization is high. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer survival.Based on this epidemiological facts, different strategies involving primary, secondary and tertiary prevention will be discussed. For prevention of HPV-positive HNSCC, emphasis will be given to vaccination strategies and novel diagnostic biomarkers for early detection. HPV-negative HNSCC are mostly represented by oral cavity cancers. In this particular context, a Working Group of international experts was convened by the International Agency for Research on Cancer (IARC) to review and assess all available evidence on the effectiveness of primary and secondary preventive interventions in reducing the incidence of and mortality from oral cancer. Available evidence will be summarized. Finally, we will address the challenge of unmet oral cancer prevention in the context of oral potentially malignant disorders (OPMD) in terms of oral cancer risk assessment and pharmacological interception approachs.In conclusion, a lot remains to be done to improve the prevention of HNSCC but significant opportunities exist that will hopefully allow in the near future to significantly decrease its morbidity, mortality, and profound impact on patient's quality of life.

Risk of Second Primary Malignancies in Melanoma Survivors: A Population-Based Study.

(1) Introduction: The association between melanoma (MM) and the occurrence of second primary neoplasms (SPNs) has been extensively studied, with reported incidence rates ranging from 1.5% to 20%. This study aims to evaluate the occurrence of SPNs in patients with a history of primary MM and to describe the factors that make the risk higher in our population. (2) Material and Methods: We conducted a prospective cohort study and calculated the incidence rates and relative risks (RR) for the development of different SPNs in 529 MM survivors from 1 January 2005 to 1 August 2021. Survival and mortality rates were obtained, and the Cox proportional hazards model was used to determine the demographic and MM-related factors that influence the overall risk. (3) Results: Among the 529 patients included, 89 were diagnosed with SPNs (29 prior to MM diagnosis, 11 synchronous, and 49 after MM), resulting in 62 skin tumors and 37 solid organ tumors. The estimated probability of developing SPNs after MM diagnosis was 4.1% at 1 year, 11% at 5 years, and 19% at 10 years. Older age, primary MM location on the face or neck, and histologic subtype of lentigo maligna mm were significantly associated with a higher risk of SPNs. (4) Conclusions: In our population, the risk of developing SPNs was higher in patients with primary MM located on the face and neck and with the histological subtype of lentigo maligna-MM. Age also independently influences the risk. Understanding these hazard factors can aid in the development of MM guidelines with specific follow-up recommendations for individuals with the highest risk.

Prognostic significance of preoperative anaemia on occurrence of regional metastases and second primary tumours in patients with early-stage oral squamous cell carcinoma

The aim of this study was to evaluate the effect of preoperative anaemia on the risk of occurrence of regional metastases and second primary tumours in patients with early-stage (cT1–T2N0M0) oral squamous cell carcinoma (OSCC) after primary surgical treatment. Consecutive patients with OSCC who were referred to University Hospital Dubrava and University Clinical Centre of Kosovo between January 1, 2000 and December 31, 2010, and who met the following criteria, were included: adult> 18 years of age; verified cT1–T2N0M0 stage; available data on clinical and laboratory work-up allowing the assessment of demographics, lifestyle/habits, anaemia, and comorbidities. The inclusion time-frame allowed a maximum potential censored observation of 15 years and minimum censored observation of 5 years (patients treated by the end of 2010). Microcytic anaemia was significantly associated with a higher risk of regional metastases (60% vs 40%, P = 0.030), with an odds ratio of 3.65 (95% confidence interval 1.33–9.97, P = 0.028). Alcohol consumption was independently associated with an increased risk of second primary tumour, with an odds ratio of 2.79 (95% confidence interval 1.32–5.87, P = 0.007). In patients with OSCC, microcytic anaemia was found to be an independent predictor of regional metastases, and alcohol consumption an independent predictor of second primary tumour.

Author’s reply to Krishnamurthy et al. and Thiagarajan

It was encouraging to note the bolstering responses from experts in the field to the recently published editorial on second primary versus recurrent tumor.[1] The editorial discussed the inconsistencies in the currently used sets of diagnostic criteria and their practical implications, focusing mainly on head-and-neck squamous cell carcinoma (HNSCC). I thank Krishnamurthy et al.[2] and Thiagarajan[3] for their letters, which not only shed light on a few more crucial observations relevant to the topic but also incited further deliberation on possible solutions to the problem at hand. In addition to the peculiar statistical and clinical issues highlighted in the editorial arising from the lack of a standardized definition of a second primary tumor and uniform criteria to distinguish it from recurrence (locally) or metastasis (distantly), there is also the question of how to determine the pathological status of the intervening mucosa. Does this accurate diagnosis mandate invasive pathological sampling of normal-looking intervening mucosa? As raised by Thiagarajan, what would be the diagnostic stand if the intervening mucosa showed dysplasia?[3] Regarding the risk of a second primary tumor, as conjectured by Krishnamurthy et al.,[2] some of the recent studies have reported an apparent protective effect of human papillomavirus (HPV) positivity in HNSCC, that contrasts with the significant increase in the risk of second primary tumors conferred by traditional risk factors like tobacco and alcohol.[4–6] This is not surprising, given the remarkable differences in the molecular mechanisms of carcinogenesis between HPV-positive and HPV-negative tobacco-related HNSCC.[7] Interestingly, in these studies, patients with oral cavity primaries and those with comorbidities were noted to have a significantly higher rate of second primary tumors, suggesting that these factors are also important determinants of the risk of developing second primary tumors in HNSCC.[4,5] As highlighted by Thiagarajan,[3] although the works of Warren and Gates from the 1930s remain the most cited criteria for defining the second primary tumor in the literature, several articles cite Theodore Billroth’s work from the 1880s as the origin of the three-point criteria.[4,5,8] However, the inability to access the original work of Billroth, and consequently, the lack of clarity about the context and components of the criteria described by him, could be some of the reasons for it not being widely adopted or cited. Nevertheless, as highlighted in the editorial,[1] despite the presence of sets of criteria endorsed by the International Association of Cancer Registries and the Surveillance, Epidemiology, and End Results program for a few decades now, researchers still prefer using the Warren and Gates criteria to define second primary tumors, probably for their simplicity and comprehensibility.[4,5] Interestingly, as discussed in both letters,[2,3] a group of researchers from The Netherlands proposed a novel and intriguing classification scheme in 2002 intending to solve the clinical predicament of distinguishing a second primary tumor from recurrent disease with the help of molecular characterization of the tumors.[9] However, not many have explored this approach, probably owing to issues with feasibility, technical challenges, and practical applicability of such a scheme in patient care, as subsequently pointed out by the experts from the International Head and Neck Scientific Group, which also included authors of the 2002 study from The Netherlands.[10] In other words, the practical utility of molecular diagnostics is yet to be streamlined and has a long way ahead. Even if made available in most large centers, standardization and universal adherence may still be challenging.[11] Thus, although molecular profiling is the future, with several added advantages that could aid in therapeutic decision-making until a sensitive and standardized set of molecular criteria are established for separating second primary tumors from recurrent and metastatic tumors, the most feasible solution currently is to standardize the existing clinical guidelines and ensure universal adherence across cancer registries and research groups. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Follow, consider, and catch: second primary tumors in acromegaly patients.

The risk of second primary tumors is increased in general cancer population, however, there is no data on acromegalic cancer patients in this regard. The aim of this study is to determine the prevalence of patients with two primary tumors among acromegalic cancer patients and to evaluate if patients with two primaries have distinct clinical characteristics or risk factors compared to those with one. This is a single-center retrospective cohort study. The study included 63 patients with at least one malignant tumor out of a total number of 394 acromegaly patients. Patients with multiple primary neoplasms were evaluated in detail. This study revealed a 16% cancer prevalence in acromegaly patients, with 14% (9/63) having two primary neoplasms. Papillary thyroid carcinoma was the most prevalent tumor in the entire cancer cohort (41%, 26/63), and in the group of patients with two primaries (44%, 4/9). Patients with two primary tumors were older than those with one when diagnosed with acromegaly (48.3 ± 16.6 vs. 43.3 ± 10.7 years), which might be attributed to a longer diagnostic delay (median of 4.5 vs. 2 years). The period between the onset of acromegaly symptoms and diagnosis was not associated with earlier cancer diagnosis. No relationship between circulating GH or IGF-I levels and the number of neoplasms was found. The development of second primary tumors in acromegalic patients with cancer diagnosis is not rare. Acromegalic cancer patients should be closely monitored for new symptoms or signs that could be associated with second primary tumors.

Risk of Second Primary Neoplasms of the Central Nervous System

PurposeSecond primary (SP) neoplasms of the central nervous system (CNS) among cancer survivors are devastating but poorly understood processes. The absolute risk, or true incidence, of developing an SP CNS tumor among cancer survivors is not well characterized. Methods and MaterialsPatients diagnosed with cancer between 1975 and 2016 were queried using the Surveillance, Epidemiology, and End Results Program. Cumulative incidence rates (CIRs) were estimated using competitive risk analysis. The effects of covariates were assessed using multivariate competitive risk regression. ResultsMore than 3.8 million patient records were extracted. The absolute risk of developing an SP CNS neoplasm at 25 years was highest among long-term survivors of CNS cancers (CIR, 6.6%). Cranial radiation increased the incidence of SP tumors in pediatric patients (25-year CIR, 5.7% vs 1.1%; P = .0012) but not adults (25-year CIR, 5.8% vs 5.0%; P = .66). Multivariate cumulative risk regression identified radiation among pediatric patients as the greatest risk for an increased CIR (subdistribution hazard ratio, 2.50; 95% CI, 1.86-3.38; P = 2e-9). Meningiomas (42.9% vs 24.1%; P = 2e-7) and glioblastomas (20.5% vs 14.5%; P = .046) represented a greater proportion of the SP CNS tumors in those who received cranial irradiation. The median age of an SP diagnosis was decreased among those who received prior radiation (41 years [interquartile range (IQR), 30-65 years] vs 49 years [IQR, 30-65 years]; P = 7e-5). ConclusionsThe risk of developing a second primary CNS neoplasm is elevated in patients with a prior CNS cancer independent of treatment history. The association between cranial radiation therapy and risk for subsequent cancers may be limited to the pediatric population.

Second Primary Neoplasms in Patients With Sebaceous Carcinoma of the Eyelid: A Population-based Study, 2000 to 2016.

To investigate the risk of second primary neoplasms (SPNs) after primary sebaceous carcinoma of the eyelid (SCE). Data on patients diagnosed with primary SCE as their first malignancy were extracted from the Surveillance, Epidemiology, and End Results database from 2000 to 2016. Observed-to-expected ratios of SPNs were calculated to estimate standardized incidence ratios (SIRs). Patients were compared with a reference population (RP) matched for age, gender, and race. Five hundred fifty-nine patients with primary SCE were identified, 16% of whom developed SPNs. SCE patients displayed a 61% increased risk of developing SPNs compared with the RP (p < 0.001). Overall, the risk of SPNs of the lungs (SIR = 1.82; p < 0.05), pancreas (SIR = 2.94; p < 0.05), salivary glands (SIR = 41.65; p < 0.001), and skin (SIR = 8.33; p < 0.05) was elevated. Only non-Hispanic Whites were at an increased risk (SIR = 1.51; p < 0.05). Patients 40-54 years old at the time of diagnosis were at the highest risk of developing SPNs compared with the RP (SIR = 3.15; p < 0.05). Women with SCE experienced an increased risk of breast cancer (SIR = 3.6; p < 0.05) and chronic lymphocytic leukemia (SIR = 8.8; p < 0.01). SCE patients are more likely to develop SPNs of the lungs, pancreas, salivary gland, and skin than the RP. Forty to fifty-four years old Caucasian patients are at the highest risk. Women are at an increased risk of developing breast malignancies and chronic lymphocytic leukemia. Clinicians should be cognizant of these risks when managing SCE patients.

Increased risk of second primary tumours in patients with oesophageal squamous cell carcinoma: a nationwide study in a Western population.

BackgroundPatients with primary oesophageal squamous cell carcinoma are at risk of developing multiple primary tumours in the upper aero digestive tract. To date, most studies are performed in the Asian population. We aimed to evaluate the risk of multiple primary tumours in the upper aero digestive tract and stomach in patients with oesophageal squamous cell carcinoma in a Western population.MethodsWe performed a nationwide, retrospective cohort study in collaboration with the Netherlands Cancer Registry. Patients with primary oesophageal squamous cell carcinoma, diagnosed between 2000 and 2016, were included. Primary endpoints were synchronous and metachronous multiple primary tumour risk.ResultsThe cohort consisted of 9058 patients, diagnosed with oesophageal squamous cell carcinoma (male: 57.3%, median age 67 years). In 476 patients (5.3%), 545 multiple primary tumours have been diagnosed. Most of them were located in the head and neck region (49.5%). Among all multiple primary tumours, 329 (60.4%) were diagnosed synchronously (<6 months after oesophageal squamous cell carcinoma diagnosis) and 216 (39.6%) metachronously (6 months). Patients with oesophageal squamous cell carcinoma had a significantly increased risk of both synchronous (standardised incidence ratio 10.95, 99% confidence interval 9.40–12.53) and metachronous multiple primary tumours (standardised incidence ratio 4.36, 99% confidence interval 3.56–5.10), compared to the general population. The median interval to metachronous second primary tumour diagnosis was 3.0 years (interquartile range 1.8–5.9).ConclusionApproximately one in 20 patients with primary oesophageal squamous cell carcinoma have a second primary tumour in the upper aero digestive tract or stomach, either at the time of oesophageal squamous cell carcinoma diagnosis or at a later stage. As second primary tumours occur at an increased risk compared to the general population, prospective studies are necessary to investigate the yield and survival benefit of screening for second primary tumours in patients with oesophageal squamous cell carcinoma.

Personalised follow-ups for patients curatively treated for squamous cell carcinoma in the oral cavity

As a result of an increase in the incidence of oral cancer and improving survival rates, the number of patients needing follow-up care will increase in the Netherlands. At present, these patients enroll in a 5-year follow-up programme aiming for early detection of recurrences or second primary tumors and improving their prognosis of life expectancy, among other things. Recurrences mostly occur in the first 2 years after treatment, whereas patients have a lifelong elevated risk of second primary tumors. 75% of second primary tumors occur outside the oral cavity and over 50% outside the head and neck area, places not routinely checked. There is no convincing evidence this 5-year follow-up programme yields survival benefits. It would therefore be better to limit follow-up care to 2 years and choose a subsequent follow-up programme better tailored to the individual patient's needs. This does not necessarily require the lead of a head and neck oncologist.

Cancer predisposition syndromes as a risk factor for early second primary neoplasms after childhood cancer - A national cohort study.

Childhood cancer patients are at increased risk of second primary neoplasms (SPNs). We assessed incidence and risk factors for early SPNs with a focus on cancer predisposition syndromes (CPSs). This cohort study used data from the Swiss Childhood Cancer Registry. We included patients with first primary neoplasms (FPNs) diagnosed before age 21 years from 1986 to 2015 and identified SPNs occurring before age 21. We calculated standardised incidence ratios (SIRs) and absolute excess risks (AERs) using Swiss population cancer incidence data, and cumulative incidence of SPNs. We calculated hazard ratios (HRs) of risk factors for SPNs using Fine and Gray competing risk regression. Among 8074 childhood cancer patients, 304 (4%) were diagnosed with a CPS and 94 (1%) developed early SPNs. The incidence of SPNs was more than 10-fold higher in childhood cancer patients than the incidence of neoplasms in the general population (SIR = 10.6, 95% confidence interval [CI]: 8.7-13.1) and the AER was 179/100,000 person-years (CI: 139-219). Cumulative incidence of SPNs 20 years after FPN diagnosis was 23% in patients with CPSs (CI: 12-41%) and 2.7% in those without (CI: 2.0-3.6%). Risk factors for SPNs were CPSs (HR = 7.8, CI: 4.8-12.7), chemotherapy (HR = 2.2, CI: 1.1-4.6), radiotherapy (HR = 1.9, CI = 1.2-2.9), haematopoietic stem cell transplantation (HR = 1.8, CI: 1-3.3), and older age (15-20 years) at FPN diagnosis (HR = 1.9, CI: 1.1-3.2). CPSs are associated with a high risk of SPNs before age 21 years. Identification of CPSs is important for appropriate cancer surveillance and targeted screening.

Second primary neoplasms in patients with primary orbital lymphoma: a population‐based study 1992 to 2016

AbstractPurposeTo investigate, in a population‐based study, the risk of developing second primary neoplasms (SPNs) after a diagnosis of primary orbital lymphoma (OL).MethodsData on a cohort of patients with a diagnosis of primary OL as their first malignancy were extracted from the Surveillance, Epidemiology, and End Results US registry from 1992 to 2016. Observed‐to‐expected ratio of developing SPNs was calculated to estimate relative risk (RR) and associated 95% confidence interval (CI), which were compared to a reference population (RP) matched for age, sex, race, and calendar year.ResultsA total of 1063 patients with primary OL were identified, 14% of whom developed SPNs. Mean age at OL diagnosis was 66 years old, while that at a SPN diagnosis was 74. There was a significant 20% excess risk of SPNs development in OL patients compared to the RP (p &lt; 0.05). Two to 11 months after OL diagnosis, there was an increased risk of respiratory tract malignancies [RR: 3.2 (95% CI: 1.2–6.9); p &lt; 0.05], while 10–15 years after diagnosis, there was an increased risk of colorectal cancer [RR: 3.0 (95% CI: 1.1–6.4); p &lt; 0.05]. Stratification by sex revealed an increased risk of prostate cancer development in males [RR: 3.4 (95% CI: 1.1–8.0); p &lt; 0.05]. Patients aged 40–59 years old experienced the greatest burden of SPNs with a significant 46% excess risk compared to the RP (p &lt; 0.05). Radiotherapy‐treated patients were at a higher risk of thyroid SPNs [RR: 3.8 (95% CI: 1.04–9.6); p &lt; 0.05].ConclusionsPatients with primary OL experience a 20% increased risk of SPNs compared to the RP. Two to 11 months and 10–15 years after OL diagnosis mark an increased risk of respiratory tract and colorectal SPNs, respectively. Male OL patients tend to more readily develop prostate malignancies than the RP. Patients 40–59 years old display the highest risk of SPNs. Radiotherapy is associated with an increased risk of developing thyroid neoplasms. Patients who are diagnosed with primary orbital lymphoma should be followed with these risks in mind.BibliographySurveillance Research Program, National Cancer Institute SEER*Stat software (www.seer.cancer.gov/seerstat) version 8.3.6.1.

Using Exhaled Carbon Monoxide as a 5th Vital Sign in an Outpatient Oncology Clinic: A Pilot Study of the Impact on Provider and Patient Engagement in Smoking Cessation Efforts

Objectives: Smoking after an HPV associated cancer diagnosis is associated with greater treatment toxicities, higher risk of treatment failure, higher risk of second primary tumors, and poorer quality of life. Yet, engagement in smoking cessation efforts remains suboptimal among patients and providers. Exhaled breath carbon monoxide (eBCO) measurement reliably identifies smokers, and CO levels reflect the intensity of an individual’s smoking behavior. We sought to evaluate the feasibility of routinely incorporating eBCO measurement in an outpatient gynecologic oncology clinic and the subsequent impact on clinician and patient engagement in smoking cessation efforts.

Development of second primary tumors and outcomes in medulloblastoma by treatment modality: A Surveillance, Epidemiology, and End Results analysis.

As treatment modalities for medulloblastoma have developed and overall survival (OS) has improved, there are relatively limited data on the impact of long-term effects such as risk of second primary tumors (SPT). To address the knowledge gap, we analyzed factors associated with the risk of SPT and OS by treatment modality for medulloblastoma. We queried the Surveillance, Epidemiology, and End Results (SEER)-18 database for patients diagnosed with medulloblastoma in 1973-2014. Patients were then grouped by age, gender, race, geographic region, histology, adjuvant treatment (no radiation [RT] and no chemotherapy [CT], RT and CT, RT alone, or CT alone), era of diagnosis (1973-1994 or 1995-2014), and survival time. Cumulative incidence, factors associated with SPT and OS were analyzed. Of 2271 patients, 146 developed SPT, of which 42 were benign. The incidence of SPT was 3.1% and 4.9% at 10 and 15 years, respectively. The incidence of SPT was 3.1% with RT + CT versus 3.7% with RT alone at 10 years. The most common site for an SPT was the central nervous system. Female gender (P=0.01) and longer OS of ≥21 years (P<0.01) were associated with higher risk of SPT. RT + CT led to better OS than RT only (66.1% and 61.4% vs 55.6% and 49.7% at 10 and 15 years) (P<0.01). Medulloblastoma patients have a relatively low risk of SPT at 10 years with treatment. Use of RT + CT led to better OS with no statistical difference in SPT compared with the RT alone.

Update of NGS analysis of Italian survey of second tumors in patients with diagnosis of GIST (gastrointestinal stromal tumor).

e23518 Background: In patients with GIST, literature reports a risk of second primary tumors between 4.5% and 33% with different distribution in the worldwide. The network of 7 italian EURACAN centers has collected clinical and molecular features of GIST patients with second primary tumors. Methods: We reviewed the clinical characteristics of 201 patients with GIST and second primary tumors in order to evaluate association between risk of dead and each possible factor, using Kaplan meier curve, log-rank test and Cox model for Hazard Ratio and it’s interval Confidence 95% estimation. Furthermore, NGS analysis ( 56 gene onco panel) in 72 patients with GIST was performed. Results: On the basis of the significant correlation previously observed between the Miettinen risk criteria of GIST (low/very low) and the incidence of second primary tumors (gastrointestinal tumors),P &lt; 0.001 (Abstr 11032 ASCO 2019), we observed in these patients a median age of diagnosis of GIST of 68, with prevalent gastric site localization ( KIT exon 11 mutation), NF1 and Lynch (kit/pdgfra WT) syndromes in the low risk subgroup. The more frequent site of second epithelial tumor in gastrointestinal tract was the colon followed by gastric, pancreatic and biliary tract. In patients with GIST with low-very low risk according Miettinen classification, after a median follow-up period of 25 years, we have observed that the gastroenteric site of second tumors occurrence is significantly related to the survival (p &lt; .0003). In the NGS analysis of the GIST we observed the pathogenetic somatic mutations in the following genes: BRCA 2 (p.Thr2125fs), but germline test negative, TP53 (p.Arg192*,p.Gly244Ser,p.His168Leu), RET (p.Lys120Asn, p.His168Leu, p.Thr930Met ), NRAS (p.Gly134Asp), CTNNB1 (p.Ser45Phe), MSH6 (P.Ala164Val), SMARCB1 (p.Arg192), VHL (p.Gly93Val), PTEN(p.Val158Ile, p.Asn323fs), STK1I (p.Arg40Cys), SMO (p.Glu194Lys), EGFR (p.Gly721Asp), ATM (p.Asp2708Asn), ERBB4 (p.Asn181Ile). Conclusions: In our analysis patients with GIST (low-very low classes according to Miettinen) have significant risk to death because of second primary tumors in gastrointestinal tract. Specific attention to gastrointestinal screening during the follow-up of GIST (low and very low risk) is required.

Tumor subtypes associated with prostate cancer (PCa) both as first and second primary tumors: A registry-based analysis.

e17528 Background: First primary tumors (FPT) generally are associated with decreased survival and, thus, reduced risk of second primary tumors (SPT). A greater than expected incidence of SPT may indicate causal factors shared in common with a particular FPT, especially if the converse also is observed, i.e. if incidence is also greater than expected when tumor sequence is reversed. We analyzed the Surveillance, Epidemiology, and End Results (SEER) cancer registry to identify tumors with higher than expected incidence in relation to PCa, both as FPT and SPT. Methods: We searched the SEER18 cancer database covering 18 geographical regions of the U.S. from 2000 to 2016. SEER*Stat software v.8.3.6 was used to calculate standardized incidence ratios (SIR) of various SPT after defined FPT. SIR compare the incidence of a particular cancer within subsets of the registry population as a ratio to the expected incidence from a comparable matched group derived from the general population. 813,712 men with prostatic FPT (1° PCa) were included in the analysis for SIR of any SPT, while 2,554,835 men with any FPT were included in the analysis for SIR of prostatic SPT (2° PCa). Results were stratified by race and latency. Reciprocal SIR (1° PCa; 2° PCa) for values with p &lt; 0.05 are reported. Results: Aggregate analysis of all tumors demonstrated lower than expected SIR for SPT, both for any SPT after 1° PCa and for 2° PCa after any FPT (0.69; 0.53). By contrast, six tumor subtypes – small intestine (1.17; 1.19), melanoma (1.05; 1.23), bladder (1.14; 2.02), kidney (1.22; 1.36), thyroid (1.27; 1.36), and chronic myelogenous leukemia (1.10; 1.15) – had bidirectionally increased secondary SIR in relation to PCa. The reciprocal increases were detected across racial subgroups for bladder, kidney and thyroid cancers. SIR tended to be highest in the early post-FPT period (2-11 mo.) with significant increases for bladder (1.49; 6.75), kidney (2.66; 1.87), and thyroid (1.61; 1.65) cancers. These three tumor types retained bidirectional increases in relation to PCa over intermediate latencies (12-119 mo.), but not beyond 120 mo. Conclusions: Overall, FPT were associated with lower than expected incidence of SPT, most likely as a result of shortened life expectancy. However, several tumors were identified that 1). occurred with higher than expected incidence after 1° PCa and 2). were associated with higher than expected incidence of 2° PCa. Further examination of the relationship of these tumors with PCa may identify mutual intrinsic or extrinsic factors that contribute to tumor development.

Relative and absolute risk of second primary neoplasms of the central nervous system.

1593 Background: Cranial radiation is known to increase the relative risk for developing a second primary neoplasm, but existing analyses do not take into account differential survival or follow-up. The absolute risk, or true incidence, of developing a second primary neoplasm in the central nervous system (CNS) is not well characterized. Methods: Patients diagnosed with cancer from between 1976 and 2016 were sampled using the Surveillance, Epidemiology, and End Results (SEER) Program. Relative risks were estimated using standardized incidence ratios (SIRs) and absolute risks were estimated using cumulative incidence (CI) functions with death as a competing risk. Among CNS primaries, comparison groups were matched by age, sex, year of diagnosis, primary histology, and lesion location. Results: Over 3.8 million patient records, including 13,167 second primary CNS tumors, were extracted from SEER. The relative risk of developing a second primary CNS neoplasm is elevated in all patients diagnosed with a CNS primary cancer (SIR = 9.6), but higher in those who received radiation (SIR = 13.1) or chemotherapy (SIR = 12.6). The absolute risk of developing a second primary CNS neoplasm at 25-years is highest in CNS and endocrine cancers (CI 1.0% and 0.50%, respectively). Among long-term ( &gt; 10-year) survivors of CNS primaries, the 25-year CI of a second primary CNS neoplasm was 4.4%. Cranial radiation increased the incidence of second primary tumors in pediatric patients (25-year CI 4.8% vs 1.2%, p = 0.007), but not adults (25-year CI 5.1% vs 4.9%, p = 0.85). Chemotherapy did not increase CI in either pediatric (25-year CI 7.0% vs 5.4%, p = 0.87) or adult (25-year CI 3.6% vs 5.8%, p = 0.11) populations. Meningiomas (39.3% vs 22.0%, p = 1e-6) and glioblastomas (21.1% vs 14.6%, p = 0.03) represent a greater proportion of the second primary CNS tumors in those who received cranial irradiation. Conclusions: The risk of developing a second primary CNS neoplasm is elevated in patients with a prior CNS cancer. Cranial irradiation increased the CI of second primary tumors in pediatric patients but did not affect adult patients. The association between radiation therapy and risk for subsequent cancers may be limited to the pediatric population.

Radiotherapy of prostate cancer: impact of treatment characteristics on the incidence of second tumors

BackgroundIt has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients.MethodsA retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and “any site”. The correlation with RT technique was analysed using log-rank test and Cox’s proportional hazard method.ResultsWith a median follow-up of 72 months (range: 9–185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9–152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07–5.47, p: .034).ConclusionsThe incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.

Craniofacial second primary tumors in patients with germline retinoblastoma previously treated with external beam radiotherapy: A retrospective institutional analysis.

The long-term survival of germline retinoblastoma patients is decreased due to the risk of second primary tumors (SPTs) that occur years after the diagnosis of retinoblastoma. This risk is related to genetic predisposition and other factors, such as the treatment of retinoblastoma by external beam radiotherapy (EBRT). We studied the incidence, risk factors, and prognosis of specific craniofacial SPTs developed within the margins of radiation field in a cohort of 209 patients with germline retinoblastoma treated with EBRT at our institution between 1977 and 2010. Clinical characteristics, survival, incidence, and histology of craniofacial SPTs were recorded. Fifty-three of the 209 patients developed 60 distinct craniofacial SPTs in irradiated field with a median time from EBRT of 16.9 years (4-35) and a median follow-up of 24.8 years (5.3-40). Osteosarcoma (33.3%) and undifferentiated sarcoma (23.3%) were the more prevalent histological entities. Benign tumors (16.7%) also occurred. The cumulative incidence of craniofacial SPTs reached 32.6% at 35 years after EBRT, and the median survival after diagnosis was five years. In our series, irradiation under 12 months of age, bilateral EBRT, or previous treatment of retinoblastoma with chemotherapy did not significantly increase the risk of craniofacial SPTs. This work presents a strong argument to avoid EBRT in the management of retinoblastoma and emphasizes the high risk and poor prognosis of specific craniofacial SPTs. This study also points to the question of the need and benefits of special programs for early detection of craniofacial SPTs in survivors of irradiated germline retinoblastoma.

The risk of second primary tumors in head and neck cancer: A systematic review.

Second primary tumors (SPTs) are a common cause of reduced life expectancy in patients treated for head and neck cancer (HNC). This phenomenon forms an area to be addressed during posttreatment follow-up. We conducted a systematic review of literature following PRISMA guidelines, from 1979 to 2019, to investigate incidence of SPTs, synchronous, and metachronous, in HNC population. Our review includes data of 456 130 patients from 61 articles. With a minimum follow-up of 22 months, mean incidence of SPTs was 13.2% (95% CI: 11.56-14.84): 5.3% (95% CI: 4.24-6.36) for synchronous SPTs and 9.4% (95% CI: 7.9-10.9) for metachronous SPTs. The most frequent site for SPTs was head and neck area, followed by the lungs and esophagus. Although with wide variations between studies, the rate of SPTs in HNC patients is high. Given the impact in the prognosis, we must develop strategies for the early diagnosis of SPTs.

Accompagnement des dépendances à l’alcool et au tabac des patients atteints d’un cancer des voies aérodigestives supérieures

Most head and neck cancers are associated with smoking and alcohol exposure. Smoking and alcohol cessation (ASC) is associated with improved quality of life, cancer therapy efficacy, decreased treatment-related and cardiovascular risks, and is expected to decrease the risk of second primary tumor. It is therefore a high priority in the plan of care. However, results of current ASC programs are disappointing and understanding the reasons of this is critical. We started a qualitative study in 6 academic centers including 3 university hospitals, one regional hospital and one comprehensive cancer center. We first interviewed surgeons and care givers involved in the management of head and neck cancers. Poor communication between stakeholders, absence of alignment of care goals between patients, surgeons and other caregivers, and low level of understanding by patients of the benefits of ASC were felt to represent frequent obstacles to successful outcome. More work is ongoing within the context of our IHNPACT umbrella protocol to identify hurdles associated with successful ASC.