Incidence Of Second Primary Tumors Research Articles

A Somatostatin Analogue, Octreotide, Inhibits the Occurrence of Second Primary Tumors and Lung Metastasis after Resection of Hepatocellular Carcinoma in Mice

Occurrence of second primary tumors and metastasis remains the major obstacles to prolonged survival of patients with primary hepatocellular carcinoma (HCC). A somatostatin analogue, octreotide, has been previously reported to inhibit the growth of human HCC xenografts in nude mice through its anti-angiogenic activity. It is therefore important to investigate whether octreotide could prevent second primary hepatomas or distant metastasis following resection of primary HCC. In this study, nude mice, bearing the human HCC xenografts with highly metastatic potential (LCI-D20) in the left liver lobe, underwent tumor resection, and received intraperitoneal administration of octreotide or saline as a control for 35 consecutive days. Compared with the control group, octreotide at the doses of 100 and 200 microg/kg/day significantly inhibited the growth (P < 0.001 and P < 0.001, respectively) and incidence of second primary tumors (P = 0.016 and P = 0.001, respectively), decreased lung metastasis (P < 0.001 and P < 0.001, respectively), and prolonged the life span (P = 0.029 and P = 0.006, respectively). Moreover, intratumoral angiogenesis quantified by microvessel density as well as serum and tissue vascular endothelial growth factor (VEGF) levels were considerably decreased in octreotide-treated animals compared to the control animals. These findings suggest that octreotide may prevent the occurrence of second primary hepatomas and lung metastasis after resection of primary HCC, which may be partially attributed to down-regulation of VEGF and subsequent reduction in tumor angiogenesis. Octreotide administration may be useful as an adjuvant therapy to improve survival of patients with HCC.

Colorectal Cancer after Breast Cancer: Magnitude of Risk in Clinical Practice and in the Literature

The aim of our study was to estimate the incidence of second primary tumors among breast cancer patients from the Division of Oncology of Andosilla Hospital (Viterbo, Italy). In particular, we studied the relationship between breast and colorectal cancer. Eligible women were those with primary invasive breast cancer who had been treated and/or followed up at our division. We compared our data with those reported in the literature. Of 114 women with breast cancer, 21 (18.5%) developed multiple primary cancers, with colorectal cancer accounting for a quarter. We found a higher incidence of colorectal cancer than reported in the literature (5% vs 0.66-1%). At the moment we are not able to explain this difference. Quite a few studies reported a link between breast and colorectal cancer, but the magnitude of the risk (standardized incidence ratio 1.3-2) does not justify a screening program for colorectal disease in breast cancer patients. However, considering that the risk is small but not negligible--along with the high incidence of colorectal adenomas described in breast cancer patients and the possible existence of common risk factors--we invite clinicians not to neglect the possibility of a colorectal cancer diagnosis in women who have had breast cancer.

High constant incidence rates of second primary neoplasms

The incidence of contralateral breast cancer is high and constant with age, around five per 1000 women who had a primary breast cancer. For other neoplasms, the pattern of incidence of second primary neoplasms with age is less known, particularly as for only a few neoplasms the site of origin is not totally removed, and hence remains at risk of a second primary. Using the dataset from the Cancer Registry of the Swiss Canton of Vaud, we show that the incidence of second neoplasms is constant with age also after oral and pharyngeal, colorectal cancers, cutaneous malignant melanoma (CMM) and basal cell carcinoma. The incidence of first primary oral and pharyngeal cancer increased 20-fold between age 30-39 and 70-89 years, whereas the incidence of second neoplasms did not increase with age. Rates of second colorectal cancer remained relatively constant with age, between 2.5 per 1000 at age 40-59 years and 3.8 per 1000 at 70 years and above. Likewise, for CMM, the age-specific incidence rates of second primary CMM did not vary, ranging between 1 and 2.5 per 1000 in various subsequent age groups. The pattern of incidence for second basal cell carcinoma was similar, with no clear rise with age. These patterns are compatible with the occurrence of a single mutational event in a population of susceptible individuals. A possible implication of these observations is that a variable, but potentially large, proportion of cancers arise in very high-risk individuals and the incidence, on average, increases at a high constant level at a predetermined age.

P53 mutation in histologically normal mucosa of the aero-digestive tract is not a marker of increased risk for second primary carcinoma in head and neck cancer patients

Head and neck cancer patients are at high risk for developing second primary tumors. This is known as field cancerization of the aero-digestive tract. In a previous study, we showed that patients with multiple primary tumors were more likely to have p53 mutations in histologically normal mucosae than patients presenting with an isolated tumor. Based on this observation, we postulated that p53 mutations in normal tissue samples of patients bearing a single primary tumor could have a clinical value as a biomarker for the risk of developing second primary tumors. Thirty-five patients presenting with a single primary tumor were followed-up for a median of 51 months (range 1 month to 10.9 years) after biopsies of histologically normal squamous cell mucosa had been analyzed for p53 mutations with a yeast functional assay at the time of the primary tumor. During this follow-up, recurrences and non-sterilization of the primary tumor, occurrence of lymph node metastases, and of second primary tumors were evaluated. Sixteen (45.7%) patients were found to have p53 mutations in their normal squamous cell mucosa, and 19 (54.3%) patients showed no mutation. No relationship was found between p53 mutations and the occurrence of evaluated events during follow-up. Notably, the rate of second primary tumors was not associated with p53 mutations in the normal squamous mucosa. The correlation between p53 mutations in histologically normal mucosae and the incidence of second primary tumors is generally low. The benefit of analyzing p53 mutations in samples of normal squamous cell mucosa in every patient with a primary tumor of the head and neck is doubtful.

Autofluorescence bronchoscopy: Clinical experience with an optimized system in head and neck cancer patients

Abstract Head and neck (H&N) cancer patients have a high incidence of second primary tumors in the tracheobronchial tree, which affects the patient prognosis and management. Diagnostic autofluorescence endoscopy (AFB) has shown promising results in the detection of early neoplastic and pre-neoplastic changes in the bronchi. We have investigated the medical and therapeutic impact of AFB in a population of 21 H&N cancer patients using a modified commercially available AFB system. That allows both white light (WL) and autofluorescence (AF) observation. Endoscopic imaging of the tissue AF was combined with an online image analysis procedure improving the discrimination between true and false positive results. Forty-one biopsies were taken on macroscopically suspicious (WL or AF positive) bronchial sites. Histopathologic analysis confirmed pre- or early neoplastic changes in 11 of these biopsies taken from eight patients. All these lesions had been AF positive upon bronchoscopy. The sensitivity for the detection of these early lesions with the AFB was 1.6 times the sensitivity of WL bronchoscopy alone. The positive predictive value (PPV) for AF was 79% (33% for WL alone) while the PPV of both methods together was 100%. We could demonstrate that AFB is efficient for the detection of second primary lesions of the bronchi in H&N cancer patients. In conclusion, AFB can be used as a simple and minimally invasive additional procedure to pre-operative or follow-up examination in this patient population.

Pituitary adenomas in northern Sweden: a study on therapy choices and the risk of second primary tumours

To present the incidence of pituitary adenomas in northern Sweden and to determine whether the incidence of second primary tumours differs from the incidence in the general population or might be related to radiotherapy. A retrospective register study. A total of 546 patients with pituitary adenomas were identified in the Cancer Registry of northern Sweden between 1958 and 2004. Only patients with histopathological verification and/or endocrine activity of the adenoma and more than 12 months of follow-up were included, resulting in 376 patients in the study. The number of patients receiving surgery and/or radiotherapy and presenting second primary tumours were registered. Standard incidence ratios (SIRs) between the observed and the expected incidence of second primary tumours were calculated. The total number of person-years at risk for a second primary tumour was 4730. Fifty-four out of 376 (14%) patients had 63 second primary tumours. Forty patients had second primary tumours diagnosed more than 12 months after diagnosis of the pituitary adenoma (expected 42.6, SIR 0.94, 95% CI 0.67-1.28). A significantly increased incidence of second primary tumours was seen in 42 men with GH-secreting adenomas. Ten second tumours were found (expected 4.55, SIR 2.20, 95% CI 1.05-4.04). A total of 261 patients received radiotherapy and 31 second primary tumours occurred after radiotherapy (expected 32.9, SIR 0.94, 95% CI 0.64-1.34). Three second primary intracranial tumours appeared within the irradiation volume (expected 0.85, SIR 3.51, 95% CI 0.71-10.36). No significant increase was found in the incidence of second primary tumours in general in patients with pituitary adenomas. An increased incidence of second primary tumours was seen in men with GH-secreting adenomas.

‘Increased incidence of secondary tumours in thyroid cancer patients’: a fact or a sophism?

In the paper by Robbert B T Verkooijen et al. (1), they described an increased incidence of second primary tumours (SPTs) in thyroid cancer patients. They found no association with iodine-131 (I-131) treatment of differentiated thyroid cancer (DTC), but surmised a common aetiology and/or genetic mechanism causing the observed increased prevalence of SPTs, especially breast cancer, in thyroid cancer patients. In concluding, they recommended close clinical follow-up for early diagnosis of SPTs in patients with DTC. The astonishing results and conclusions of Verkooijen et al. prompted us to search our own database; it contained 1087 patients (73% females, 27% males) with the diagnosis of thyroid cancer. The follow-up period ranged between a minimum of 1 year and a maximum of 30 years (mean 7G5 years); the mean age of the patients was 51G16 years and 103 patients had passed away. Therapeutic doses of I-131 had been given to 933 patients, and 154 had very small primary lesions of DTC with a very low risk of tumour recurrence, and therefore received no I-131 therapy. We included patients with medullary carcinoma in our analysis, in contrast to Verkooijen et al., but otherwise age, gender distribution, histopathology, ablation doses and time points of treatment were comparable with the group reported by Verkooijen et al. In our group, we found 125 additional SPTs in 112 patients (11 patients had three tumours, 1 patient had four tumours), yielding a percentage of 11.5% vs 14.2% (40 out of 282 patients). Fifty-five tumours had occurred several years prior to the diagnosis of DTC (mean 8.4 years). Thus, our data analysis ultimately revealed 5% of patients who had developed an SPT (following the diagnosis of DTC and treatment) when compared with 7% of those reported by Verkooijen et al. These data are in accordance with others, such as Bhattacharyya et al. and Canchola et al. (2, 3). Verkooijen et al. reported a significantly increased standardized incidence ratio (SIR 3.95) for SPTs only when patients with breast cancer before thyroid cancer were included; their SIR for SPTs following DTC overall was 1.13, which is nearly the same as our value of 1.06. Sadetzki et al. (4) found an elevated risk in women with breast cancers for DTCs. Cengiz et al. (5) also observed

A Population-Based Analysis of Second Primary Cancers After Irradiation for Rectal Cancer

To investigate the possible association between pelvic irradiation for rectal cancer and subsequent second primary cancers. A population-based analysis of 20,910 individuals with rectal cancer from the Surveillance, Epidemiology, and End Results registry, for whom follow-up times were at least 5 years, was performed. Kaplan-Meier estimates for the development of second cancers within irradiated and nonirradiated cohorts provided a comparison that accounted for censored data. Cox proportional hazards analyses were further conducted to compensate for patient and tumor-related factors. A total of 656 (12%) and 2368 (16%) second primary cancers were enumerated from the irradiated and nonirradiated cohorts, respectively, with the proportion of second primary cancers within the irradiated cohort being significantly decreased (P < 0.001) on crude analysis. However, Kaplan-Meier and Cox analyses revealed no significant difference between the 2 cohorts when all second primary cancer sites were considered together (hazard ratio = 1.02; 95% confidence interval [CI], 0.92-1.12). Proportional hazards analysis for specific second primary sites revealed a decreased risk after pelvic irradiation for cancer of the prostate (hazard ratio = 0.63; 95% CI, 0.48-0.84), and an increased risk for cancers of the uterine corpus & cervix (hazard ratio = 2.5; 95% CI, 1.6-4.0). Second primary cancers after irradiation for rectal cancers appear relatively infrequent compared with the background incidence of spontaneous cancers, and should not factor into treatment decisions for this older population. We hypothesize that the incidence of second primary tumors within adjacent organs could represent a balance between the radiation-induction of tumors and the radiation-inhibition of spontaneously occurring tumors.

Non‐smoking and non‐drinking patients with head and neck squamous cell carcinoma: a distinct population

To recognize specific clinicopathological characteristics of non-smoking and non-drinking (NSND) head and neck squamous cell carcinoma (HNSCC) patients. This can increase our knowledge regarding a potentially different carcinogenesis in these patients. Retrospective analysis of data for 195 NSND patients with HNSCC and comparison with data for patients with HNSCC obtained from the Netherlands Cancer Registry. Compared with all HNSCC patients in the Netherlands, our NSND patients with HNSCC were typically female (n = 142; 73%vs 26%), old at disease presentation (mean 73 years vs 64 years), and had tumors mainly of the oral cavity (n = 130; 66%vs 25%). Most tumors were stage I (n = 67; 34%) and stage IVA (n = 59; 30%). The incidence of second primary tumors (SPTs) was high (n = 32; 16%), mainly occurring in the oral cavity (n = 26; 13%). Our study confirms that NSND HNSCC patients have different clinicopathological characteristics from those of the overall HNSCC population; however, the frequency of SPTs is as high in NSND patients as in patients who smoke and drink alcohol. More research, and particularly molecular data are needed to obtain a better understanding of head and neck cancer in NSND patients.

The incidence of second primary tumors in thyroid cancer patients is increased, but not related to treatment of thyroid cancer

The aim of the present study is to assess the prevalence of second primary tumors in patients treated for thyroid cancer. Furthermore, we wanted to assess the standardized risk rates for all second primary tumors, but especially for breast cancer, as data in the literature indicate an excessive risk in differentiated thyroid cancer (DTC) patients for this tumor. We included consecutive patients, who received ablation treatment with I-131 at the Leiden University Medical Center between January 1985 and December 1999 (n = 282). The mean period of follow-up was 10.6 +/- 4.1 years. Thirty-five of the 282 patients (12.4%) had a second primary tumor (SPT), either preceding or following the diagnosis of thyroid cancer. Five other patients had three primary tumors, including DTC. As a result, 40 additional tumors were found in this group, revealing an overall prevalence of 14.2%. Twenty tumors (7.1%) preceded the thyroid cancer with a mean interval of 5.7 years (range: 0.5-22.0 years), whereas 20 tumors (7.1%) occurred after this tumor with a mean interval of 6.7 years (range: 1.0-15.0 years). In 13 female patients, breast cancer was found as SPT. The standardized incidence rate (SIR) for all cancers after the diagnosis of DTC in this study population was not increased (1.13; confidence interval (CI): 0.68-1.69). However, we found an increased SIR of 2.26 (CI: 1.60-3.03) for all cancers either following or preceding DTC, which is mainly caused by a SIR of 3.95 (CI: 2.06-6.45) for breast cancer. Patients with DTC have an overall increased standardized incidence rate for second primary tumors, but not for second primary tumors following I-131 therapy. These findings suggest a common etiologic and/or genetic mechanism instead of a causal relation.

Changing Failure Patterns in Oropharyngeal Squamous Cell Carcinoma Treated With Intensity Modulated Radiotherapy and Implications for Future Research

Review the University of Iowa experience with intensity modulated radiation treatment (IMRT) in oropharyngeal squamous cell carcinoma. From January 2000 to July 2004, 66 patients with oropharyngeal cancer were treated with IMRT, 62 with definitive IMRT and 4 postoperative IMRT. Three target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 were 70 to 74 Gy, 60 Gy, and 54 Gy, respectively, for definitive IMRT, and 60 to 66 Gy, 60 Gy, and 54 Gy, respectively, for postoperative IMRT. Median follow-up was 27.3 months and all living patients had a follow-up of at least 11.5 months. The 3-year estimate of locoregional progression free survival was 98.8%. However, there is a high incidence of distant metastasis with a 3-year estimate of distant metastasis-free survival of 80.4%. In addition, there is a high incidence of second primary tumor. The 3-year overall survival and 3-year disease-free survival were 78.1% and 64.4%, respectively. Treatment was well tolerated with 1 death resulting from treatment toxicity. IMRT offers an excellent locoregional control for oropharyngeal cancer patients. Failure patterns have changed with an increased portion of patients who failed distantly, either with metastasis or second primary tumor. Therefore, survival for these patients is still poor. Future research should focus on identifying patients at high risk of distant diseases and developing effective systemic treatment and prevention for distant diseases.

Segundos tumores primarios en el cáncer escamoso de cabeza y cuello

IntroductionThe development of second primary tumors (SPT) in patients with head and neck squamous cell carcinoma (HNSCC) has become an increasingly important factor in clinical treatment decisions. PurposeTo define favourable clinical characteristics for overall survival, in patients with SP head and neck cancer. Material and methodRecords of 633 patients with SCC treated from 1984 to 2004 were reviewed to describe clinical characteristics of the SPT. ResultsThe overall incidence of SPT was 11%. The incidence of the index tumors was as follows: supraglottic cancer 21% and oral cancer 16%. The most common SPT occurred in head and neck area in 47%, lung in 32% and esophagus in 11%. Second primary was associated with a poor 5 years survival in patients with HN-SCC (23 versus 53% in control group). ConclusionBecause of the high rate of second primary tumors, protocols including chemoprophylaxis should be investigated. Prevention and early detection are indicated.

Risk factors for developing a second upper aerodigestive cancer after radiotherapy with or without chemotherapy in patients with head-and-neck cancers: An exploratory outcomes analysis

The objective was to assess the influence of treatment-related and patient-related factors on the risk of developing a second primary tumor (SPT) of the upper aerodigestive tract (UADT) in patients with locoregionally advanced nonmetastatic carcinomas of the head-and-neck region. The data of 521 patients with a minimum follow-up of 1 year were pooled: 224 patients from the Swiss Group for Clinical Cancer Research (SAKK) 10/94 trial, treated with 1.2 Gy b.i.d. to 74.4 Gy, and randomized to receive or not to receive simultaneous chemotherapy with cisplatin (excluding nasopharyngeal and maxillary sinus carcinomas); and 297 patients from Geneva, all treated with accelerated radiotherapy with concomitant boost to 69.9 Gy and predominantly cisplatin-based concomitant chemotherapy in 33% of patients (including 21 patients with nasopharyngeal carcinomas). An exploratory analysis using competing risk methodology was performed. A total of 65 SPT of the UADT were observed after a median observation time of 4.7 years. The overall risk of experiencing an SPT of the UADT at 10 years in the presence of all other possible events was estimated to be 33%. There were no SPTs after treatment for nasopharyngeal carcinoma. In a multivariate logistic regression analysis, there was no difference in occurrence of SPT at 3 years with respect to the administration of chemotherapy (p = 0.31), age (p = 0.62), performance status (p = 0.61), gender (p = 0.27), presence of nodal disease (p = 0.51), or T stage (p = 0.72). However, patients treated with concomitant boost had fewer SPTs (p = 0.0093). Our data do not suggest that addition of chemotherapy to radiotherapy influences the incidence of second cancers in patients with head-and-neck cancer. The difference in the incidence of SPT between the two radiotherapy schedule groups merits further exploration.

Chemoprevention of Head and Neck Cancer With Retinoids

To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma. Randomized, double-blind, placebo-controlled trial. Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to enter appropriate patients into this trial. One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment. Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for 1 year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years. The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured. There was no significant difference in the occurrence of second primary disease (P = .90), the recurrence of primary disease (P = .70), or disease-free time (P = .80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival. With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.

Nonocular second primary tumors after retinoblastoma: retrospective study of 111 patients treated by electron beam radiotherapy with or without TEM.

The objective of this study was to assess the role of various clinical and treatment factors involved in the long-term incidence of nonocular second primary tumors following retinoblastoma. The study was based on 111 patients treated between 1963 and 1977 according to the same radiotherapy protocol (electron beam radiotherapy) alone or in combination with triethylene melamine (TEM). Various statistical methods were used to obtain the actuarial survival curve, the cumulative incidence of second primary tumors, and comparisons of patient groups and subgroups. The 5-, 10-, 20-, and 30-year survival rates were 75%, 70%, 63%, and 55% with a follow-up of 23 to 35 years. The study reports the various parameters concerning 111 children and 17 second primary tumors: sex, age at treatment, histology of the retinoblastoma and second primary tumors, site of second tumors (anatomic and compared with irradiation field), radiation dose, time to onset, and chemotherapy with or without TEM. The results are discussed and compared with the data reported in the literature. Electron beam radiotherapy at a dose of 45 Gy does not eliminate the risk of nonocular second primary tumors. TEM also does not modify survival or the overall incidence of second primary tumors, but significantly increases the risk of second primary tumors outside the irradiation field.

13-cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group

Patients with squamous cell carcinoma of the head and neck (HNSCC) after being treated radically remain at high risk for both recurrent and second primary tumours. 13-cis retinoic acid (13-cRA) was demonstrated to reverse pre-malignant lesions of the oral cavity and to reduce the incidence of second primary tumours in patients treated radically for HNSCC. Synergism between retinoids and interferon in tumoural cell lines have been demonstrated. Based on these data, the Italian Head and Neck Chemoprevention Study Group started a randomized chemoprevention study in patients radically treated for stage III and IV HNSCC. From February 1992 to January 1996, 267 patients were randomized: 126 were allocated to the control group, 126 were randomized to receive 13-cRA at a dose of 0.5 mg/kg per day per os and 15 patients have been assigned to the group of 13-cRA plus interferon alpha2a (IFN-alpha2a) at a dose of 3,000,000 UI 3 times a week (randomization in this arm interrupted due to administrative financial problems). The mean follow-up was 39 months. The 5-year actuarial survival was 58.9% for patients of the 13-cRA group and 57.2% for those of the control group (P=0.94). Among evaluable patients, disease progression was observed in 45 of 123 patients (36.6%) of the 13-cRA group and in 42 of 124 (33.9%) of the control group. The 5-year actuarial relapse-free survival was 48.9% for the 13-cRA group and 55.6% for the control group (P=0.62). Adverse effects, mostly of grade I were reported in 69.4% of treated patients (haematologic disorders, mucositis, conjunctivitis, cutaneous toxicity, hypertriglyceridemia and hypercholesterolemia). Only 5 patients (4.1%) reported grade III-IV toxicity. Low-dose of 13-cRA given for 1 year is ineffective as chemoprevention in patients with radically treated HNSCC.

Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.

The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy. We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis. Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2) Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.

β-carotene supplementation in patients radically treated for stage I-II head and neck cancer: Results of a randomized trial

This study was aimed at evaluating the efficacy of beta-carotene in improving survival (S) and in disease-free survival (DFS) and reducing the incidence of second primary tumors (SPT) in patients with a radically treated stage I-II squamous head and neck tumors. Eligible patients were randomly allocated to receive beta-carotene (n=104) or no treatment (n=110). beta-carotene was administered at the dose of 75 mg/day for 3-month cycles within one month intercycle intervals for a 3-year period. The 3-year compliance to the beta-carotene was 68.7%. Only eight patients reported drug-related toxicity (7.8%). The median follow-up of all patients was 59 months. The median follow-up was 61 months (range 1-116 months) in the beta-carotene and 58 months (1-123 months) in the control group. The 10-year DFS was 75.7% for the patients in the beta-carotene and 74.3% for those in the control group (P=0.56). The 10-year S was 85.9% in the beta-carotene group and 80.9% in the control group (P=0.20). beta-carotene supplementation had no significant effect on the incidence of second primary tumors (RR=0.99; 95% C.I. 0.28-3.44). A statistically non-significant 40% reduction in the risk of death among subjects assigned to the beta-carotene compared to the controls was observed (RR=0.60; 95% C.I. 0.26-1.38). No increase in the death from cardiovascular diseases was observed among patients treated with beta-carotene. Our results might support the hypothesis that an adequate beta-carotene treatment could be potentially associated with a decreased risk of death in these patients.

Second primary tumors following adjuvant therapy of resected stages II and IIIa non-small cell lung cancer

The occurrence of second primary tumors (SPTs) following adjuvant therapy for resected stages II and IIIa non-small cell lung cancer (NSCLC) was investigated. Data regarding SPTs were prospectively collected in all patients accrued to Eastern Cooperative Group Oncology E3590 (a phase III trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC). Four hundred eighty-eight patients were accrued to the study, 242 to the RT arm and 246 to the CRT arm. Median follow-up was 73 months. Thirty patients (6.1%) developed 33 SPTs, 20 in the RT arm and ten in the CRT arm. Ten SPTs occurred within the upper aerodigestive tract, six in the RT arm and four in the CRT arm. Twenty-three SPTs occurred in other organs, 17 in the RT arm and six in the CRT arm. Median time to detection of a SPT for those patients randomized to RT and CRT was 43 and 36 months, respectively. The incidence of SPTs was 1.8% per patient-year of follow-up. Excluding skin tumors, the relative risk of death following diagnosis of a SPT for patients randomized to the CRT arm as compared with those randomized to RT alone was 2.26 (95% confidence interval, 0.78–5.58, P=0.12). Patients are at risk for developing a SPT following resection of stages II and IIIa NSCLC. The majority of SPTs occur outside the aerodigestive tract. Following development of a non-skin SPT, the survival difference between patients who had received adjuvant CRT and those treated with adjuvant RT alone was not significant.

Invited commentary

The management of patients with small, peripheral lung cancers, but with very limited pulmonary reserve or other serious co-morbid conditions, continues to be a formidable challenge. Several large series have concluded that segmental and/or wedge resections of stage I lung cancers (excluding small cell carcinoma) are associated with a higher incidence of local/regional recurrence when compared with patients with similar tumors undergoing a lobectomy. I agree with others that for patients with clinical stage I lung cancer, “less-than lobectomy” resections should be reserved for compromised patients. In the current paper, the authors have added their voices to the growing chorus advocating the option of implanting brachytherapy seeds along the pulmonary resection margins in an attempt to limit local recurrence. This is an intuitively attractive idea, and apparently can be performed safely. However, this strategy focuses only on those cancer cells remaining undetected in the surrounding lung parenchyma. The possibilities of “drop metastases” in the pleural space to a remote sites on the surface of the lung, implants into the wound (especially port sites), and recurrences arising from tumor cells in the parenchymal lymphatics and in unresected bronchopulmonary or mediastinal nodes are other manifestations of recurrent tumor that would not be addressed. Indeed, when faced with only a CT scan and a positive needle aspirate, it can be difficult if not impossible to establish the spatial relationship between the recurrent tumor and the original margin of resection. This is precisely why, in our paper, I defined local/regional recurrence so broadly. Had we not done so, another reviewer of our clinical experience could have concluded that segmental resections predispose to a high incidence of second primary tumors, since many were judged to be remote from the pulmonary resection margin. I agree with the author’s conclusion. Establishing whether or not brachytherapy reduces the incidence of local recurrence will require a larger collection of carefully selected patients studied and followed for several years.