Incidence of late recurrence and second primary cancers 5-10 years after non-metastatic colorectal cancer.

The fraction of patients who are cancer-free survivors 5 years after curative-intended surgery for colorectal cancer (CRC) is increasing, suggesting that extending surveillance beyond 5 years may be indicated. Here we estimate the incidence of late recurrence, metachronous CRC, and second primary cancers 5-10 years postoperative. All patients resected for UICC stage I-III CRC in Denmark through 2004-2013 were identified. Through individual-level linkage of nationwide health registry data, recurrence status was determined using a validated algorithm. Cancer-free survivors 5 years after surgery, were included. Cumulative incidence functions (CIF) of late recurrence, metachronous CRC, and second primary cancer 5-10 years postoperative were constructed. Subdistribution hazards ratios (sHR) were computed using Fine-Gray regression. Among 8883 patients, 370 developed late recurrence (5-10-year CIF = 4.1%, 95%CI: 3.7%-4.6%), 270 metachronous CRC (5-10-year CIF = 3.0%, 95%CI: 2.7%-3.4%), and 635 a second primary cancer (5-10-year CIF = 7.2%, 95%CI: 6.7%-7.7%). The risk of late recurrence was reduced for patients operated in 2009-2013 compared to 2004-2008 (2.9% vs. 5.6%, sHR = 0.52, 95% CI: 0.42-0.65). The risk of metachronous CRC was likewise reduced from 4.1% to 2.1% (sHR = 0.50, 95%CI: 0.39-0.65). While the risk of second primary cancer did not change between 2009-2013 and 2004-2008 (7.1% vs. 7.1%, sHR = 0.98, 95% CI: 0.84-1.15). Using nation-wide 10-year follow-up data, we document that the incidences of late recurrence and metachronous CRC are low and decreasing from 2004 to 2013. Thus, despite increasing numbers of long-term cancer survivors, the data do not advocate for extending CRC-specific surveillance beyond 5 years.

Second primary non-breast cancers in young breast cancer survivors.

PURPOSE: We evaluated the incidence, timing, and risk factors for second primary non-breast cancers (SPNBC) among young breast cancer (BC) survivors. METHODS: This study included participants of the Young Women's BC Study (YWS) who were diagnosed with stage 0-III BC between 2006 and 2016 and age 40 or younger at diagnosis (N = 1,230). Patient characteristics, treatment information, and clinical events were collected via serial surveys. Tumor and treatment data were obtained from medical record review. Five- and 10-year risks of SPNBCs were estimated via the cumulative incidence function, considering death, metastasis, or second primary BC as competing events. Fine and Gray subdistribution hazard models estimated subdistribution hazard ratios (sHRs) and 95% confidence intervals (CI) for SPNBC risk based on risk factors including demographics, germline genetics, primary BC characteristics, and treatments. RESULTS: Among 1,230 women, over a median follow-up of 10.1 years, 47 patients (4%) developed an SPNBC. Types of malignancy included melanoma (n = 10), thyroid (n = 10), ovarian (n = 4), sarcoma (n = 4), uterine (n = 3), rectal (n = 3), bladder (n = 2), cervical (n = 2), head/neck (n = 2), lung (n = 2), lymphoma (n = 2), pancreatic (n = 2), and renal (n = 1). Five and 10-year cumulative incidence were 1.4% and 3.2%, respectively. Median time between primary BC and SPNBC was 7.3 years. No patient factors, primary tumor characteristics, or treatments were statistically significantly associated with SPNBC in univariable or multivariable models. CONCLUSION: In this population, five-year cumulative incidence was higher than that reported among healthy women under 50 years of age, highlighting the importance of long-term surveillance for new non-breast cancers in young adult BC survivors.

HLA diversity unveils susceptibility and organ-specific occurrence of second primary cancers: a prospective cohort study.

BACKGROUND: Up to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence. METHODS: We analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles. RESULTS: During a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59-0.89; females: HR 0.81, 95% CI 0.70-0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03-1.56; females: HR 1.35, 95% CI 1.07-1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females. CONCLUSIONS: These results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC.

Histology-specific standardized incidence ratio improves the estimation of second primary lung cancer risk.

BACKGROUND: Lung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer is unexpectedly low in countries that follow international multiple primary (IARC/IACR MP) rules when compared to the USA, where distinct rules are employed. IARC/IACR rules rely on histology-dependent documentation of SPC with the same location as the first cancer and only classify an SPC when tumors present different histology. Thus, SIR might be underestimated in cancer registries using these rules. This study aims to assess whether using histology-specific reference rates for calculating SIR improves risk estimates for second primary lung cancer (SPLC) in LC survivors. METHODS: We (i) use the distribution of histologic subtypes of LC in population-based cancer registry data of 11 regional cancer registries from Germany to present evidence that the conventional SIR metric underestimates the actual risk for SPLC in LC survivors in registries that use IARC/IACR MP rules, (ii) present updated risk estimates for SPLC in Germany using a novel method to calculate histological subtype-specific SIRs, and (iii) validate this new method using US SEER (Surveillance, Epidemiology, and End Results Program) data, where different MP rules are applied. RESULTS: The adjusted relative risk for lung cancer survivors in Germany to develop an SPLC was 2.98 (95% CI 2.53-3.49) for females and 1.15 (95% CI 1.03-1.27) for males using the novel histology-specific SIR. When using IARC/IACR MP rules, the conventional SIR underestimates the actual risk for SPLC in LC survivors by approximately 30% for both sexes. CONCLUSIONS: Our proposed histology-specific method makes the SIR metric more robust against MP rules and, thus, more suitable for cross-country comparisons.

Variation in patterns of second primary malignancies across U.S. race and ethnicity groups: a Surveillance, Epidemiology, and End Results (SEER) analysis.

PURPOSE: One in six incident cancers in the U.S. is a second primary cancer (SPC). Although primary cancers vary considerably by race and ethnicity, little is known about the population-based occurrence of SPC across these groups. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) 12 data and relative to the general population, we calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPC among 2,457,756 Hispanics, non-Hispanic Asian American/Pacific Islanders (NHAAPI), non-Hispanic black (NHB), and non-Hispanic whites (NHW) cancer survivors aged 45 years or older when diagnosed with a first primary cancer (FPC) from 1992 to 2015. RESULTS: The risk of second primary bladder cancer after first primary prostate cancer was higher than expected in Hispanic (SIR = 1.18, 95% CI: 1.01-1.38) and NHAAPI (SIR = 1.41, 95% CI: 1.20-1.65) men than NHB and NHW men. Among women with a primary breast cancer, Hispanic, NHAAPI, and NHB women had a nearly 1.5-fold higher risk of a second primary breast cancer, while NHW women had a 6% lower risk. Among men with prostate cancer whose SPC was diagnosed 2 to <12 months, NHB men were at higher risk for colorectal cancer and Hispanic and NHW men for non-Hodgkin's lymphoma. In the same time frame for breast cancer survivors, Hispanic and NHAAPI women were significantly more likely than NHB and NHW women to be diagnosed with a second primary lung cancer. CONCLUSION: Future studies of SPC should investigate the role of shared etiologies, stage of diagnosis, treatment, and lifestyle factors after cancer survival across different racial and ethnic populations.

The risk of second malignancies following prostate cancer radiotherapy in the era of conformal radiotherapy: a statement of the Prostate Cancer Working Group of the German Society of Radiation Oncology (DEGRO).

A significant number of prostate cancer patients are long-term survivors after primary definitive therapy, and the occurrence of late side effects, such as second primary cancers, has gained interest. The aim of this editorial is to discuss the most current evidence on second primary cancers based on six retrospective studies published in 2021-2024 using large data repositories not accounting for all possible confounding factors, such as smoking or pre-existing comorbidities. Overall, prostate cancer patients treated with curative radiotherapy have an increased risk (0.7-1%) of the development of second primary cancers compared to patients treated with surgery up to 25 years after treatment. However, current evidence suggests that the implementation of intensity modulated radiation therapy is not increasing the risk of second primary cancers compared to conformal 3D-planned radiotherapy. Furthermore, increasing evidence indicates that highly conformal radiotherapy techniques may not increase the probability of second primary cancers compared to radical prostatectomy. Consequently, future studies should consider the radiotherapy technique and other confounding factors to provide a more accurate estimation of the occurrence of second primary cancers.

Risk for second primary cancers among pediatric and young adult melanoma survivors.

BACKGROUND/OBJECTIVES: Second primary cancers (SPCs) are a leading cause of morbidity and mortality among cancer survivors. In this study, we aimed to characterize the incidence of SPCs among pediatric and young adult survivors of CM. METHODS: Using the Surveillance, Epidemiology, and End Results Program data spanning 2000-2018, we calculated standardized incidence ratios (SIR) to assess SPC risk in all pediatric (0-18 years) and young adult (19-29 years) patients with a first primary cancer diagnosis of CM. RESULTS: Of 7,169 total CM survivors, 632 (8.82%) developed a SPC, corresponding to a 5-fold increased risk (standardized incidence ratio [SIR] 4.98; 95% confidence interval [CI] 4.60-5.38) compared to the general population. There was a highly elevated risk for second primary melanoma across all age groups (SIR 32.5; 95% CI 29.7-35.6), constituting the majority of SPC diagnoses (N = 485). Infants diagnosed with CM before 1 year of age had the highest risk for any SPC (SIR 164; 95% CI 19.8-592) and young adults diagnosed at 25-29 years had the lowest risk (SIR 4.64; 95% CI 4.19-5.13). SPC incidence was highest within the first year of CM diagnosis (SIR 27.5; 95% CI 23.7-31.6) and progressively decreased with time. CONCLUSIONS: Variation exists in the incidence and type of SPC according to age among pediatric and young adult survivors of CM.

[About a case of primary laryngeal mucosal melanoma in a patient with medical history of oropharyngeal squamous carcinoma]. / À propos d'un cas de mélanome muqueux primitif laryngé chez un patient présentant un antécédent de carcinome épidermoïde de l'oropharynx.

INTRODUCTION: Primary laryngeal mucosal melanoma is a rare tumour with a poor prognosis. Its often difficult diagnosis should rule out laryngeal metastatic localization of cutaneous melanoma. CASE PRESENTATION: We report a case of primary laryngeal mucosal melanoma diagnosed in a 65-year-old man, treated 6 years previously with radio-chemotherapy and surgery for squamous cell carcinoma of the right lateral oropharyngeal region. The definitive diagnosis of primary laryngeal mucosal melanoma was made on the resection specimen, whereas the initial biopsy of the epilaryngeal mass discovered during the patient's surveillance had concluded that it was a laryngeal recurrence of the known squamous cell carcinoma. DISCUSSION: Through this case, we propose to remind the main characteristics and the diagnostic pitfalls of these tumours.

Nodular type but not vitamin D levels increases the risk of second primary cancers in melanoma patients: An observational study of 663 patients.

BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.

Nodular Type but Not Vitamin D Levels Increases the Risk of Second Primary Cancers in Melanoma Patients: An Observational Study of 663 Patients. / [Artículo traducido] El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes.

BACKGROUND: Vitamin D deficiency associates with the risk of developing many diseases, including cancer. At the molecular level, vitamin D appears to have an antineoplastic effect. However, the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results. This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers (SPC). MATERIALS AND METHODS: A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022. The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan-Meier curves and differences were assessed by log-rank tests. Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia. RESULTS: Out of 663 patients, 34 developed a non-cutaneous SPC. There was no statistically significant association between vitamin D levels and non-cutaneous SPC development (log-rank, p=0.761). Age>60 years, stage III/IV, and nodular melanoma subtype were significantly associated with the development of a SPC. After multivariate analysis, only age>60 years (HR 3.4; HR CI 95%: 1.5-7.6) and nodular melanoma subtype (HR 2.2; HR CI 95%: 1.0-4.8) were included in the final model. CONCLUSIONS: Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients. However, age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development.

Second primary cancer among 217702 colorectal cancer survivors: An analysis of national German cancer registry data.

With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person-years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor-related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12-1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17-1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4-fold in this group (SIR males 4.51, 95% CI 4.04-5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62-4.48, AER = 77.0). Primary tumor-related factors associated with SPC risk were right-sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.

Incidence of second primary cancers among survivors of childhood cancer: A population-based study, Osaka, Japan, 1975-2015.

Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0-14 years during 1975-2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan-Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.

Hematologic malignancies following immune checkpoint inhibition for solid tumors.

Immune checkpoint inhibition (ICI) can induce durable responses in patients with advanced malignancies. Three cases of hematological neoplasia following ICI for solid tumors have been reported to date. We present five patients treated at our tertiary referral center between 2017 and 2021 who developed chronic myeloid leukemia (two patients), acute myeloid leukemia, myelodysplastic syndrome and chronic eosinophilic leukemia during or after anti-PD-1-based treatment. Molecular analyses were performed on pre-ICI samples to identify baseline variants in myeloid genes. We hypothesize that PD-1 blockade might accelerate progression to overt myeloid malignancies and discuss potential underlying mechanisms.

Long-term outcomes in patients with Burkitt lymphoma older than 65 years: an analysis of the Texas Cancer Registry.

Burkitt lymphoma (BL) is an extremely aggressive but curable subtype of non-Hodgkin lymphoma. While younger patients have excellent outcomes in response to aggressive chemoimmunotherapy, the rarity of this disease in older patients and limitations caused by age, comorbidities, and performance status may negate survival advantages. This analysis assessed outcomes of older adults with BL through data provided by the Texas Cancer Registry (TCR). Patients ≥65 years with BL were assessed. Patients were dichotomized into 1997-2007 and 2008-2018. Median overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan-Meier methodology, and covariates including age, race, sex, stage, primary site, and poverty index were analyzed using Pearson Chi-squared analysis. Odds ratio (OR) with 95% confidence intervals (CI) was used to assess factors contributing to patients not offered systemic therapy. P value <0.05 was considered statistically significant. Non-BL mortality events were also categorized. There were 325 adults, 167 in 1997-2007 and 158 in 2008-2018; 106 (63.5%) and 121 (76.6%) received systemic therapy, a trend that increased with time (p = 0.010). Median OS for 1997-2007 and 2008-2018 was 5 months (95% CI 2.469, 7.531) and 9 months (95% CI 0.000, 19.154) (p = 0.013), and DSS was 72 months (95% CI 56.397, 87.603) (p = 0.604) and not reached, respectively. For patients that received systemic therapy, median OS was 8 months (95% CI 1.278, 14.722) and 26 months (95% CI 5.824, 46.176) (p = 0.072), respectively, and DSS was 79 months (95% CI: 56.416, 101.584) and not reached, respectively (p = 0.607). Age ≥75 years (HR 1.39 [95% CI 1.078, 1.791], p = 0.011) and non-Hispanic whites (HR 1.407 [95% CI 1.024, 1.935], p = 0.035) had poorer outcomes, and patients at the 20-100% poverty index (OR 0.387 [95% CI 0.163, 0.921], p = 0.032) and increasing age at diagnosis (OR 0.947 [95% CI 0.913, 0.983], p = 0.004) were less likely to receive systemic therapy. Of 259 (79.7%) deaths, 62 (23.9%) were non-BL deaths, and 6 (9.6%) of these were from a second cancer. This two-decade analysis of older Texas patients with BL indicates a significant improvement in OS over time. Although patients were more likely to receive systemic therapy over time, treatment disparities existed in patients residing in poverty-stricken regions of Texas and in advancing age. These statewide findings reflect an unmet national need to find a systemic therapeutic strategy that can be tolerated by and augment outcomes in the growing elderly population.

Significant risk of second primary cancer among laryngeal squamous cell carcinoma patients even after 20 years.

BACKGROUND: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe. METHODS: Patients diagnosed with primary LSCC from 1953-2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included. RESULTS: A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52-1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19-11). The corresponding SIR for women was 1.47 (95% CI: 1.15-1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36-9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49-2.01 and EAR 16.8 per 1000 PY, 11.88-23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36-3.95 and EAR 0.80 per 1000 PY, 0.55-1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13-6.78). CONCLUSION: Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.

Although prior research on the risk of second primary cancer (SPC) among laryngeal squamous cell carcinoma (LSCC) patients has been conducted in other regions, the European perspective remains notably underrepresented. Moreover, studies on the subject focusing especially on LSCC are, even globally, only a few. The present study, with over 6000 LSCC patients followed-up over six decades, consists of the largest reported cohort of LSCC patients in Europe, and with the longest follow-up. Patients with LSCC as a primary cancer have a 60% excess risk for an SPC, which remains significantly elevated even 20 years after the diagnosis of the first primary cancer, especially for those with a tobacco/alcohol-related cancer. Healthcare professionals should be aware of the SPC risk among LSCC survivors who should be counseled about this phenomenon.

Clinical course of longer than five years after definitive radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.

The risk of second primary cancer after nasopharyngeal cancer: a systematic review.

PURPOSE: Second primary cancers (SPCs) after nasopharyngeal cancer (NPC) are rare, but have an impact on the follow-up of this patient population. The aim of this study is to systematically review the literature to determine the prevalence and most typical sites of SPCs after NPC. METHODS: We searched the databases of PubMed, Web of Science, and Scopus for articles on SPCs after NPC. The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed. RESULTS: This review includes data on 89 168 patients with NPC from 21 articles. The mean occurrence for SPCs was 6.6% and varied from 4.9% in endemic areas to 8.7% in non-endemic areas. The most frequent locations of SPCs were oral cavity, pharynx, nose and paranasal sinuses, esophagus and lung. CONCLUSION: There is an increased risk for a SPC after NPC management, especially in non-endemic areas. However, their mean rate is lower than after other head and neck carcinomas.

Risk of second primary cancer in patients with head and neck squamous cell carcinoma: a systemic review and meta-analysis.

OBJECTIVES: Second primary cancer is a common event in patients with head and neck squamous cell carcinoma. However, the incidence and relevant factors vary by studies. We conducted a systematic review and meta-analysis of observational studies to estimate the incidence and relevant risk factors. MATERIALS AND METHODS: PubMed and Web of Science were searched for studies published between January 2000 and December 2020 that reported the incidence of SPC in HNSCC patients. Per 1000-person-year incidence and odds ratios were used to estimate the incidence and potential risk factors. Due to the high heterogeneity, random-effects models were used to estimate the incidence and 95% confidence interval. RESULTS: Seven thousand seven hundred thirteen articles were identified from the databases, in which 60 studies were included in this meta-analysis. The pooled incidence of the total, synchronous, and metachronous SPC in patients with HNSCC were 29.116 per 1000-person-year, 6.960 per 1000-person-year, and 26.025 per 1000-person-year, respectively. The head and neck region was the most common area where SPC occurred, followed by the lung (7.472 per 1000-person-year) and upper digestive tract (2.696 per 1000-person-year). Smoking, alcohol consumption, betel quid chewing, primary cancer of T1-2, and N0 were risk factors, while HPV infection (OR 0.47, 95% CI 0.30-0.72) was the protective factor. CONCLUSIONS: SPC is frequently observed in HNSCC patients and had great impact on the prognosis. The findings could promote a more individualized follow-up strategy for SPC in HNSCC patients. CLINICAL RELEVANCE: This systemic review and meta-analysis provide sufficient evidence for the establishment of the follow-up strategy for head and neck squamous cancer patients.

Association of radiotherapy for prostate cancer and second primary colorectal cancer: a US population-based analysis.

BACKGROUND: Radiotherapy (RT) is a common treatment for prostate cancer, yet the risk of second primary colorectal cancer (SPCRC) in patients with prostate cancer undergoing RT has not been adequately studied. METHODS: This study employed a population-based cohort design using the US Surveillance, Epidemiology, and End Results (SEER) database to identify individuals diagnosed between January 1975 and December 2015. The cumulative incidence of SPCRC was estimated using Fine-Gray competing risk regression. Poisson regression analysis was used to estimate the risk associated with RT. Survival outcomes of patients with SPCRC were evaluated using the Kaplan-Meier method. RESULTS: A total of 287,607 patients diagnosed with prostate cancer were identified. The cumulative incidences were higher in patients who did not receive RT (2.00%) compared to those who underwent RT (2.47%) after 25 years. After adjustment for multiple variables, RT was associated with an increased risk of developing combined SPCRC (adjusted HR 1.590). Additionally, the overall survival was significantly lower in patients who developed colorectal cancer after receiving RT as compared to those who did not receive RT. CONCLUSION: These findings underscore the need for diligent long-term monitoring and effective management strategies to detect SPCRC in patients treated with RT for prostate cancer.

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

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 3­year 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.