Risk Of Second Neoplasms Research Articles

Multiple primary cancer: an increasing health problem. Strategies for prevention in cancer survivors

This study was set to look for associations between the sites of the first and subsequent tumours in patients with multiple primary cancer (MPC) diagnosed from 1975 to 2002 in the reference hospital of a Spanish northern region, and propose prevention strategies. Patient and tumour variables were measured. Crude and standardized incidence rates per 100 000 inhabitants were obtained, and the association between MPC incidence and time was analysed by means of lineal regression. Relative risks were calculated to analyse associations between tumour sites. A total of 2737 MPC cases were registered (male/female ratio = 2). The percentage of MPC with respect to the total cancer increased from 1.78% in the 1975-1979 period to 7.08% in the 2000-2002 period (R(2) = 0.92; P = 0.003). Great increase of incidence by time was found (R(2) = 0.90; P = 0.004). Breast, prostate and bladder cancers increase risk of second tumour in female genital organs [RR 4.78 (3.84-5.93)], urinary system [RR 3.69 (2.89-4.69)] and male genital organs [RR 3.76 (2.84-4.69)] respectively. The MPC incidence is increasing. Interventions for MPC prevention, according to the European Code against Cancer, should be implemented early after the first cancer principally if patients suffer breast, bladder, prostate, larynx and colon cancers.

A female survivor of childhood medulloblastoma presenting with growth-hormone-induced edema and inflammatory lesions: a case report

IntroductionThe improved survival of children with brain tumors has increased concerns about treatment-related sequelae. Growth hormone deficiency is frequently observed after craniospinal irradiation for medulloblastoma. It has been widely reported that growth hormone replacement therapy does not increase the risk of second tumors, but there are reports in the literature of growth hormone, and its downstream mediator insulin-like Growth Factor 1, having an important proinflammatory action. There are few reports, however, on the "in-vivo" induction of edema and symptomatic inflammatory lesions during replacement therapy.Case presentationWe report the case of a 7-year-old girl treated for metastatic medulloblastoma who developed growth hormone deficiency 2 years after oncological treatment.Three months after replacement therapy, magnetic resonance imaging showed exacerbation of her brain edema, which was already present after oncological treatment. We consequently suspended the growth hormone until a new magnetic resonance image obtained 3 months later documented a reduction of the inflammatory areas. We then re-introduced somatotropin at lower doses with no further increase in brain edema in subsequent radiological controls.ConclusionThis case and its iconography suggest a strong association between growth hormone administration and the exacerbation of inflammatory reactions within the tumor bed. Replacement therapy should be carefully monitored in this particular subset of patients.

Late Effects after Autologous Hematopoietic Cell Transplantation

Over 30,000 autologous hematopoietic cell transplants (HCT) have been performed yearly during the past decade. With improvement in supportive care, few patients succumb to early treatment complications; hence, more attention is being paid to causes of late complications and death. However, interpretation of the data that exist is difficult as the definition of ‘‘late’’ varies by study, as does the patient population, underlying diseases, HCT mobilization and conditioning regimens, stem cell sources, and duration of follow-up (Table 1). Most importantly, the methods used to estimate the incidence of late complications over time are different or are not explained in sufficient detail. Some studies report relative risk or standardized mortality compared with the general population. Other studies report an acturial estimate (which ignores competing risks and thus may overestimate the incidence), whereas others report cumulative incidence calculations.

Risk of second tumor in intracranial germinoma patients treated with radiation therapy: the Johns Hopkins experience

We reviewed the risk of second tumor (ST), both malignant and benign, in germinoma survivors followed at the Johns Hopkins Hospital (JHH). Between 1977 and 2002, 27 patients with intracranial germinoma were treated with radiation therapy (RT). In the presence of competing events, a cumulative incidence function of ST was estimated using the minimal time interval from the date of diagnosis to the date of ST, date of death, or date of last follow-up. Five patients (18%) developed a ST of which 4 (15%) were malignant. One developed a benign falcine meningioma. The cumulative incidence of ST was 9% at 11 years (95% CI, 0-22%). The relative contributions of RT and patient susceptibility to a ST cannot be determined but suggests the need for long-term surveillance, including testicular self-exams in male germinoma survivors. Current trials of chemotherapy and reduced RT dose and volume offer the prospect of a lower risk of treatment-induced ST.

Risk of second primary malignancies and causes of death in patients with adenocarcinoma and carcinoid of the small intestine

We studied risk of second malignancies and causes of death in 1829 cases of adenocarcinoma and 3055 cases of carcinoid tumours in the small bowel reported to the Swedish Cancer Registry from 1960 through to 2000. Data on causes of death were analysed as from 1966 whereas data on second tumours was available during the whole registry-period. Follow-up was available until 2001. Standard mortality ratio (SMR) and standard incidence ratio (SIR) were calculated. Female patients with adenocarcinoma had increased risk of acquiring cancer in the female genital organs (SIR 3.2; 95% confidence intervals (CI) 1.9–5.0) and breasts (SIR 2.7; 95% CI 1.1–5.4). Both sexes combined had increased risk of second tumours in the gastrointestinal tract (SIR 1.5; 95% CI 1.1–2.1) and skin (SIR 4.6; 95% CI 1.2–12). Men with carcinoid tumour had increased risk of prostate cancer (SIR 2.8; 95% CI 1.6–4.6). Increased risk was seen for both sexes with carcinoid for malignant melanoma (SIR 6.3; 95% CI 2.7–12), malignant skin tumours (SIR 3.6; 95% CI 1.7–6.7) and malignancies of endocrine organs (SIR 2.3 95% CI 1.3–3.8). Patients with adenocarcinoma had increased risk of dying from malignant diseases other than the primary cancer (SMR 9.5; 95% CI 8.6–10) and gastrointestinal disease (SMR 2.6 95% CI 1.6–4.2). The cohort with carcinoid had higher than expected risk of dying from malignant disease (SMR 4.3; 95% CI 4.0–4.6), gastrointestinal disease (SMR 2.8; 95% CI 2.1–3.6) and cardiovascular disease (SMR 1.1; 95% CI 1.0–1.3). The increased risk of second malignant tumours is an indication of common aetiology, or possibly, a general vulnerability to malignant disease for these patients. A detailed analysis of causes of death in a population-based cohort of small intestinal malignancies has not been presented before in the literature.

Secondary Malignancies after Treatment of Aggressive Non-Hodgkin Lymphoma: A GISL Cohort Study on 1259 Patients.

BACKGROUND Secondary malignancies have been associated with Non Hodgkin Lymphoma (NHL) treatment. Nevertheless few analyses have addressed this issue focusing on aggressive lymphoma. Aims of this study were to determine the incidence and the risk factors for developing secondary cancer during long term follow up of patients treated for aggressive lymphoma.METHODS For the purpose of this study we identified in the GISL database, 1259 naïve patients with histologically confirmed diagnosis of aggressive NHL. Observed cancer were classified by site. The incidence numbers of second neoplasia was compared to the incidence of malignancies in the Italian population. The standardized incidence ratio was calculated from the ratio between observed and expected number of cancers. Absolute excess risk was calculated by subtracting the expected from the observed cases and dividing by the person-years at risk. The Time Free 2nd Tumour (TF2T) was measured from the end of the first treatment to last follow-up or date of diagnosis. Cumulative incidences were estimated either with a Kaplan-Meier estimate or by Gooley's method. Effects of potential risk factors on second cancer rates were examined in a Cox proportional-hazard model.RESULTS The cohort consisted of 1259 patients enrolled in GISL trials in the period 1988–2003, accounting for 6180 person-year at risk of second tumor. Median age at diagnosis was 58 years. All patients were treated with chemotherapy either alone or in combination with radiotherapy. During follow up, 44 patients (3.5%) developed a second cancer. Twelve out of 44 patients developed hematological malignancies and 32 solid tumors, including 7 lung cancer, 6 colorectal cancer, 4 prostate cancer and 15 other type of cancers. The median time for developing second tumors was 42 months. The risk of secondary malignancy overall was not increased. The analysis of risk by cohort of age at diagnosis of second cancer showed an excess of risk for the cohort age 20–39 and 40–59 years. Cumulative incidence of second malignancy, estimated by Kaplan Meier and by Gooley's method at 5, 10 and 15 years was 3.2%, 6.9% and 13.8%, and 2.7%, 5.2% and 9.6%, respectively. By univariate analysis we observed a significant negative impact on TF2T for age at first treatment and only marginally significant for elevated LDH level. Further, we performed a Cox regression analysis with gender, age at 1st treatment and LDH >UNL that showed the prognostic ability of these variables in predicting the risk of second tumour. We divided the log(HR) predicted from multivariate analysis, at the 33° and the 66° percentiles to obtain a score system. We observed three groups with significant difference (p< .0001) in the risk of developing second cancers.CONCLUSIONS Our results showed that the risk of second malignancy overall was not increased in patients treated for aggressive lymphoma. Cancer risk was age-related, as demonstrated by the excess of risk observed in the cohort age 20–39 and 40–59 years. Further, utilizing age, male gender and LDH in a Cox regression analysis, we demonstrated the prognostic value of these variables and we produced a score system able to identify groups with different risk of developing second malignancies.

Autologous Stem Cell Transplantation for Chronic Lymphocytic Leukemia

Autologous stem cell transplantation (ASCT) has been intensively investigated for treatment of patients with chronic lymphocytic leukemia (CLL) during recent years. To assess the potential therapeutic value of ASCT for CLL, the present article aims at answering the following crucial questions: (1) Does ASCT have curative potential? (2) What is the therapeutic potential of ASCT in terms of disease control in relation to toxicity? (3) What is the role of ASCT in the current arsenal of CLL treatment modalities? Evidence from clinical and minimal residual disease (MRD) studies suggests that ASCT has curative potential in only a few patients, if any. Nevertheless, ASCT might be capable of prolonged disease control even in CLL with poor-risk features. Uncontrolled prospective studies have indicated the superiority of ASCT over alkylator and fludarabine monotherapy but not necessarily over purine analogue cyclophosphamide or antibody combinations. A significant risk of secondary neoplasms, in particular myelodysplasias, has to be taken into account. Therefore, ASCT cannot be considered as standard treatment for CLL and should be performed only in the context of clinical trials.

Increased risk of larynx cancer in heterozygous carriers of the I171V mutation of the NBS1 gene

The high incidence of multiple primary tumors (MPT) is a significant problem in head and neck tumor treatment. Recent studies suggest that carriers of heterozygous mutations in the NBS1 gene have an increased risk of malignant tumor development. The aim of our research was to assess the frequency of NBS1 mutations in patients with larynx cancer only (LC) and with MPT. The MPT group consisted of patients with one cancer localized to the larynx (primary or second) and another at another site. DNA from 175 patients with LC and 93 patients with MPT was analyzed using the single-strand conformation polymorphism method and direct sequencing. We found nine carriers of the I171V mutation among these 268 cancer patients and only one carrier among 500 population controls (0.2%). Four carriers of the I171V mutation were detected among 175 LC patients (2.3%) and five among 93 patients with MPT (5.4%). The frequencies of the I171V mutation carriers in LC and MPT patients were significantly higher than in controls (odds ratio [OR] = 11.7, confidence interval [CI] 1.3-105.2, P = 0.0175 and OR = 28.35, CI 3.27-245.7, P = 0.0005, respectively). In one individual with LC, a novel molecular variant, c.1222 A > G (p.K408E), was identified. No carriers of R215W or 657del5 NBS1 mutations were found in the present study. These findings imply that heterozygous carriers of the I171V mutation are prone to the development of larynx cancer and may, in addition, display an increased risk of second tumors at other sites.

Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice

Diabetes mellitus (DM) is a chronic disease that is characterized by deteriorating glycemic control. The disease is known to be caused by imbalance between reactive oxygen species (ROS) and antioxidant defense systems. Hyperglycemia is commonly observed in a wide variety of diseases, including cancer. Although, therapy against glycemic control, is used in all these diseases, the diabetic cancer patients are on additional therapy with anticancer drugs. The objective of present study was to study if Glucophage (metformin), a very popular antidiabetic agent can avert the mutagenicity and lipid peroxidation caused by adriamycin (ADR), which is a commonly used cytotoxic drug. The experimental protocol included oral treatment of mice with different doses (62.5, 125 and 250 mg/kg day) of metformin for 7 days. Some mice in each group were injected i.p. with ADR (15 mg/kg). In each case animals were killed, 30 or 24, 48 and 72 h after the last treatment and femurs were excised for cytological studies by micronucleus test. Additional experiments on estimation of glutathione (GSH) and malondialdehyde (MDA) were undertaken in blood and serum, respectively. Twenty-four hour after the treatment, blood from each mouse was collected from heart and preserved for analysis. The results obtained revealed that pretreatment with metformin: (i) reduced the ADR-induced frequency of micronuclei without any alteration in its cytotoxicity and (ii) protected against the ADR-induced increase and decrease of MDA and GSH, respectively. The exact mechanism of action is not known, however, the inhibition of ADR-induced clastogenicity and lipid peroxidation by metformin may be attributed to the antioxidant action of the latter. Our results demonstrate that metformin might be useful to avert secondary tumor risk by decreasing the accumulation of free radicals and inhibition of mutagenicity.

Cancer in adolescents and young adults (AYA) in North Netherlands (1989–2003): Increased incidence, stable survival and high incidence of secondary tumors

9538 Background: Lack of improvement in survival in AYA cancer patients as compared to children has led to increased awareness of this young population. We performed a population-based study of the incidence and survival of primary tumors and incidence of second tumors in patients 12–24 years, diagnosed in North Netherlands. Methods: Patients, diagnosed 1989–2003, classified according to Birch, were retrieved from the regional cancer registry and were divided into age groups (12–15, 16–19, 20–24). Age-specific incidence rates per 100,000 were calculated using population data from Statistics Netherlands. Three-year moving means of incidence were calculated for the three age groups. 5-years survival over time for males (M) and females (F) was calculated; difference in survival was assessed with log-rank test. Results: From 1989–2003 1,118 patients were diagnosed: lymphoma 22.9%, germ-cell malignancies 14.5%, melanoma 13.7%, carcinoma 12.7%, sarcoma 11.7%, CNS tumors 11.5%, leukaemia 10%. The total age-specific incidence rates per 100,000 were: M:13.4 (12–15 yrs), 26.9 (16–19 yrs), and 27.5 (20–24 yrs) and F:13.9, 20.7, 20.7. M/F ratio was 1.32. Between 1999–2003 a remarkable high incidence of Hodgkin's lymphoma in 16–19 yrs (M 9.4, F 7.6), germ cell malignancies 14.1 (M, 20–24), and melanoma 7.0 (F, 20–24) was found. The estimated annual percent change in incidence was 2.15% (p=0.001) overall. Multivariate analysis of the incidence showed a significant increase by age and year of diagnosis. The 5 years-survival was 0.80, 0.80 and 0.82 for the three age groups. Survival did not change significantly during the study period, except for a better survival for leukemias (p=0.04). With a follow-up of 8.7 years the relative risk of secondary tumors was 34.98 (23.06- 50.89; p&lt;0.05). Conclusions: Between 1989 and 2003 the total incidence of cancer in AYA increased. Except for leukaemia survival was stable over time. No difference in survival between the age groups (12–15;16–19; 20–24) was found. From 1999–2003 a remarkable high incidence of Hodgkin's lymphomas (M, 16–19), germ cell malignancies (M, 20–24) and melanomas (F, 20–24) was observed. The relative risk of a secondary tumor in this young cohort was 35-fold increased. No significant financial relationships to disclose.

Allograft treatment increases risk of second tumour

Patients undergoing an allograft for haematological cancers, especially those 40 years of age or older, are at increased risk of developing a second cancer compared with the general population. The risk is even higher for patients whose donor was female, according to a large retrospective study (Cancer published online Nov 27, 2006; DOI:10.1002/cncr.22375).

Second Malignant Neoplasm in Patients With Osteosarcoma of the Extremities Treated With Adjuvant and Neoadjuvant Chemotherapy

We evaluated the rate of second malignancies in 1205 patients with osteosarcoma of the extremity treated at our Institution with different protocols of adjuvant and neoadjuvant chemotherapy. Twenty-six patients (2.15%) developed a second malignant neoplasm at a median of 7.6 years (1 to 25 y) after primary osteosarcoma treatment. Of these, 2 developed a third cancer which were not considered in the series. Second neoplasms were leukemia (10), breast (7), lung (2), kidney (2), central nervous system cancer (2), soft tissue (1), parotid (1), and colon (1). The rate of second neoplasms was significantly higher in female patients, and the latent period shorter in hematologic tumors compared with solid tumors. Ten of these 26 patients are disease free at a median of 7.7 years (range 1 to 15 y) after the last treatment. The rate of second malignancies observed in the osteosarcoma group was significantly higher than that observed in the control group of 1160 patients with benign tumors treated in the same period at our Institute (2.2% vs. 0.8%, P<0.009). Our study showed that the risk of second neoplasm within 15 years increased and then leveled off and that although secondary solid tumors could be explained as unrelated cases, leukemias seem to be over represented.

Joint effect of mutagen sensitivity and insulin-like growth factors in predicting the risk of developing secondary primary tumors and tumor recurrence in patients with head and neck cancer.

Early-stage head and neck cancer patients are at high risks for tumor recurrence and secondary primary tumor (SPT) development. We hypothesized that latent genetic instability and proliferation potential may be associated with elevated risks of SPT and recurrence. We conducted a nested case-control study within a randomized, placebo-controlled chemoprevention trial in patients with early-stage head and neck cancer. We compared prediagnostic bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures (as an indicator of latent genetic instability) between 298 cases (patients with SPT/recurrence) and 693 controls (patients without SPT/recurrence). We also determined the joint effects of latent genetic instability and elevated proliferation potential [indicated by serum insulin-like growth factor (IGF) level] in modulating the risk of SPT and recurrence. In the Cox proportional hazards model, patients with higher mutagen sensitivity (using a cutoff of > or =0.50 breaks per cell) exhibited a significantly increased risk of developing SPT/recurrence [hazard ratio, 1.38; 95% confidence interval (95% CI), 1.02-1.86]. Cases also exhibited significantly higher levels of IGF-I and IGF-binding protein-3 than controls (P = 0.022 and 0.042, respectively). Moreover, there were joint effects between mutagen sensitivity and IGFs in modulating SPT/recurrence risk. Using patients with low IGF-I level and low mutagen sensitivity profile as the reference group, the odds ratios of developing SPT/recurrence for patients with high IGF-I level alone, high mutagen sensitivity alone, and both high IGF-I level and high mutagen sensitivity were 2.85 (95% CI, 0.92-8.82), 3.92 (95% CI, 1.28-11.97), and 6.16 (95% CI, 2.03-18.71), respectively. A similar joint effect was observed for mutagen sensitivity and IGF-binding protein-3 level. This is the largest prospective study to evaluate mutagen sensitivity as a prognosis marker in head and neck cancer because mutagen sensitivity data were derived from baseline samples drawn before the development of SPT or tumor recurrence. The results also show for the first time that latent genetic instability and elevated proliferation potential jointly elevate the risk of second tumors in early-stage head and neck cancers.

Growth hormone (GH) use appears to increase the risk of second neoplasms among childhood cancer survivors, but the risk appears to decrease with increasing length of follow-up,

Growth hormone (GH) use appears to increase the risk of second neoplasms among childhood cancer survivors, but the risk appears to decrease with increasing length of follow-up,

Growth hormone (GH) use appears to increase the risk of second neoplasms among childhood cancer survivors, but the risk appears to decrease with increasing length of follow-up,

Growth hormone (GH) use appears to increase the risk of second neoplasms among childhood cancer survivors, but the risk appears to decrease with increasing length of follow-up,

Growth Hormone Treatment and Risk of Second Neoplasms in the Childhood Cancer Survivor

GH deficiency is common in childhood cancer survivors. In a previous report, although we did not find an increase in the risk of disease recurrence in survivors treated with GH, GH-treated survivors did have an increased risk of developing a second neoplasm (SN) (rate ratio, 3.21). In this analysis, we have reassessed the risk of GH-treated survivors developing an SN after an additional 32 months of follow-up. We conducted a retrospective cohort multicenter study. Among a total of 14,108 survivors who were enrolled in the Childhood Cancer Survivor Study, a retrospective cohort of 5-yr survivors of childhood cancer, we identified 361 who were treated with GH. We assessed the risk of developing an SN. During the extended follow-up, five new SN developed in survivors treated with GH, for a total of 20 SN, all solid tumors. Using a time-dependent Cox model, the rate ratio of GH-treated survivors developing an SN, compared with non-GH-treated survivors, was 2.15 (95% confidence interval, 1.3-3.5; P < 0.002). Meningiomas were the most common SN (n = 9) among the GH-treated group. Although cancer survivors treated with GH appear to have an increased risk of developing SN compared with survivors not so treated, the elevation of risk due to GH use appears to diminish with increasing length of follow-up. Continued surveillance is essential.

Second Primary Tumors in Neurofibromatosis 1 Patients Treated for Optic Glioma: Substantial Risks After Radiotherapy

Optic pathway gliomas (OPGs) are the most common CNS tumor in neurofibromatosis 1 (NF1) patients. We evaluated the long-term risk of second tumors in NF1-related OPGs after radiotherapy. We reviewed 80 NF1 OPG patients from two NF1 clinics to evaluate the long-term risk of developing subsequent nervous system tumors, with or without radiotherapy. Fifty-eight patients were assessable for second tumors. Nine (50%) of 18 patients who received radiotherapy after their OPGs developed 12 second tumors in 308 person-years of follow-up after radiotherapy. Eight (20%) of 40 patients who were not treated with radiotherapy developed nine tumors in 721 person-years of follow-up after diagnosis of their OPGs. The relative risk of second nervous system tumor after radiotherapy was 3.04 (95% CI, 1.29 to 7.15). There is a significantly increased risk of second nervous system tumors in those NF1 patients who received radiotherapy for their OPGs, especially when treated in childhood. Thus radiotherapy should only be used if absolutely essential in children with NF1.

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n = 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver, kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.

DNA Repair Gene Polymorphisms and Risk of Second Primary Neoplasms and Mortality in Oral Cancer Patients

We tested the hypothesis that polymorphisms in genes involved in DNA repair pathways are associated with the development of second primary neoplasms of the upper aerodigestive tract (UADT), as well as mortality, in patients previously diagnosed with oral squamous cell cancer (OSCC). DNA specimens from 279 OSCC patients who had participated in two previous population-based case-control studies were assayed for the following polymorphisms: X-ray repair cross-complementing (XRCC) 1 Arg399Gln, XRCC3 Thr241Met, xeroderma pigmentosum complementing group D (XPD) Lys751Gln, and O-methylguanine- DNA methyltransferase (MGMT) Leu84Phe and Val143Ile. Baseline demographic information was obtained from personal interviews and tumor characteristics and treatment were obtained from cancer registry files. Cox proportional hazards models were used to calculate hazards ratio (HR) estimates for each polymorphism in relation to the risk of developing second primary neoplasms at any site, UADT, and head and neck. HRs were also determined for associations with all-cause mortality and oral cancer specific mortality. A significant increased risk of second neoplasms (all sites combined, as well as for UADT sites and for head and neck squamous cell cancers) was observed among XRCC3 241Met allele homozygotes (HR 2.65-3.44, P < .02). No significant association with the development of second neoplasms was observed for the XRCC1 399Gln, XPD 751Gln, or MGMT 84Phe or 143Ile alleles. Although no associations with oral cancer-specific mortality were observed, we found a significant inverse association between all-cause mortality and possessing at least one copy of the XRCC1 399Gln allele (HR 0.68, 95% confidence interval [CI] 0.47-0.97, P = .03), as well as a suggestion of a direct association between all-cause mortality and having one copy of the XRCC3 241Met allele (HR 1.39, 95% CI 0.95-2.03, P = .09). Polymorphisms in the DNA repair enzyme gene XRCC3 241Met was associated with an increased risk of second neoplasms, and polymorphisms of the XRCC1 399Gln gene were associated with a decreased risk of all-cause mortality in patients with primary OSCC. These findings require confirmation in other populations before the clinical implications can be considered.

High-Dose Therapy and Autologous Hematopoietic Stem-Cell Transplantation Does Not Increase the Risk of Second Neoplasms for Patients With Hodgkin's Lymphoma: A Comparison of Conventional Therapy Alone Versus Conventional Therapy Followed by Autologous Hematopoietic Stem-Cell Transplantation

To determine the incidence of second malignancies among patients with Hodgkin's lymphoma (HL) treated with autologous hematopoietic stem cell transplantation (AHSCT) compared with patients receiving conventional therapy alone and to identify potential risk factors for their occurrence. We analyzed data on 1,732 consecutive patients with HL treated at the British Columbia Cancer Agency from 1976 to 2001, including 202 patients undergoing AHSCT. The median follow-up duration was 9.8 years for the whole cohort, 9.7 years for those patients treated with conventional therapy, and 7.8 years from AHSCT. The cumulative incidence of developing any second malignancy 15 years after therapy for HL was 9% (risk ratio = 3.5; P < .001); however, the incidence did not differ between those patients receiving conventional therapy alone compared with those undergoing AHSCT (10% and 8%, respectively; P = .48). In multivariate analysis, the only factor significantly associated with an increased risk of developing any second neoplasm or solid tumor was age > or = 35 years (P < .0001). An increased risk of therapy-induced acute myeloid leukemia and therapy-induced myelodysplastic syndrome was seen for patients aged > or = 35 years (P = .03) and stage III/IV (P = .04). Patients with HL are at increased risk of developing a second neoplasm. However, those patients undergoing AHSCT do not seem to be at greater risk compared with those patients receiving conventional therapy alone, at least during the first decade after therapy.