Infradiaphragmatic Radiotherapy Research Articles

Selected Articles from This Issue

Physical activity and body mass index (BMI) are well established risk factors of colorectal cancer. Whether physical activity can counteract adverse obesity-induced metabolic profiles, including inflammation, remains unclear. Using data from the ColoCare Study, Himbert and colleagues tested associations of individual and combined physical activity and BMI groups with pro-inflammatory biomarkers in the largest cohort of colorectal cancer patients to date. The authors identified BMI as the key driver of inflammation, yet, biomarker levels were higher among inactive colorectal cancer patients across BMI groups. Results suggest that physical activity may reduce obesity-induced inflammation among colorectal cancer patients.Hodgkin lymphoma (HL) survivors (HLS) treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer (CRC). Ykema, Gini, and colleagues investigated the cost-effectiveness of CRC surveillance in Dutch HLS to determine the optimal surveillance strategy for different HL subgroups. The authors adjusted well-established MISCANColon model to reflect the HL survivor population. Subsequently the model was used to evaluate benefits, harms and costs of a range of potential surveillance strategies. CRC surveillance in HL survivors at increased risk for CRC (treated with IRT and/or procarbazine-containing chemotherapy) is cost-effective and should commence earlier than in the general population. For all examined HL subgroups, FIT surveillance was the most cost-effective strategy.Multiple myeloma disproportionately affects individuals of African descent, occurring more often in Black populations compared to White. Cicero and colleagues investigated the prevalence of monoclonal gammopathy of undetermined significance (MGUS), the precursor to myeloma, in 386 Black South African men. They found MGUS in 8.03% of their cohort, nearly 1.6-fold higher than the historic White Olmsted County males. Moreover, they explored the association between MGUS and various clinical factors, notably determining a correlation between MGUS and HIV status, as well as cigarette use. Their study demonstrates that racial disparities in MGUS exist and may be associated with potentially modifiable risk factors.This study by Chien and colleagues proposed methods for adapting risk models, with or without polygenic score, for another population without prospective cohorts to help alleviate the health disparities caused by advances in absolute risk models. The authors adapted the lung cancer risk model PLCOM2012 for Taiwan, by forming an age-matched case-control study of ever-smokers, synthesizing a dataset resembling the population of cancer-free ever-smokers in 2010, and estimating the number of ever-smoking lung cancer patients in 2011–2016. The adapted PLCOT models had high performance in calibration, discrimination, and clinical usefulness, and could be used to counsel individuals and design screening programs in Taiwan. The methods could be applicable to other cancer models.

Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy.

Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups. The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG). Overall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG). Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy. Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.

Involved Site Radiotherapy Extends Time to Premature Menopause in Infra-Diaphragmatic Female Hodgkin Lymphoma Patients - An Analysis of GHSG HD14- and HD17-Patients.

IntroductionConsolidation radiotherapy in intermediate stage Hodgkin´s lymphoma (HL) has been the standard of care for many years as involved field radiotherapy (IFRT) after chemotherapy. It included initially involved region(s). Based on randomized studies, radiation volumes could be reduced and involved site radiation therapy (ISRT) became the new standard. ISRT includes the initially affected lymph nodes. In young adults suffering from HL, infertility and hypogonadism are major concerns. With regard to these questions, we analyzed the influence of modern radiotherapy concepts such as consolidating ISRT in infradiaphragmatic involvement of HL after polychemotherapy.Patients and MethodsFive hundred twelve patients treated within German Hodgkin Study Group (GHSG) HD14 and HD17 trials were evaluated. We analyzed log-adjusted follicle-stimulating-hormone (FSH)- and luteinizing-hormone (LH)-levels of HD14-patients with infradiaphragmatic radiotherapy (IDRT) in comparison with HD14-patients, who had a supradiaphragmatic radiotherapy (SDRT). In a second step, we compared IFRT with ISRT of female HD17 patients regarding the effects on ovarian function and premature menopause.ResultsWe analyzed FSH- and LH-levels of 258 female and 241 male patients, all treated with IFRT. Of these 499 patients, 478 patients had SDRT and 21 patients had IDRT. In a multiple regression model, we could show that log-adjusted FSH (p=0.0006) and LH values (p=0.0127) were significantly higher after IDRT than after SDRT. The effect of IDRT on gonadal function was comparable to two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc). We compared the effect of IFRT with ISRT in thirteen female HD17 patients with infradiaphragmatic (ID) involvement. The mean ovarian dose after ISRT was significantly lower than after IFRT. The calculated proportion of surviving non-growing follicles (NGFs) increased significantly from 11.87% to 24.48% in ISRT compared to IFRT, resulting in a significantly longer calculated time to menopause. The younger the age at therapy, the greater the absolute time gain until menopause.ConclusionInfradiaphragmatic IFRT impairs gonadal function to a similar extent as two cycles of BEACOPPesc. In comparison, the use of ISRT target volume definition significantly reduced radiation dose to the ovaries and significantly extends the time interval from treatment to premature menopause.

Long-term neurotoxicity and quality of life in testicular cancer survivors-a nationwide cohort study.

To evaluate neurotoxicity in testicular cancer survivors (TCSs) years after treatment and secondly the influence of neurotoxicity on quality-of-life (QoL). We identified 2234 TCSs who completed the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire. QoL was evaluated with the European Organization for Research and Treatment of Cancer QLQ-C30. Patients were grouped according to treatment strategy: surveillance (N = 1113), infradiaphragmatic radiotherapy (N = 301), cisplatin-etoposide-bleomycin (BEP) (N = 759), and more than one line of treatment (MTOL) (N = 61). Association of treatment modality with long-term neurotoxicity was analyzed with ordinal logistic regression. Secondly, associations between neurotoxicity and QoL were analyzed in BEP-treated patients. Analyses were age-adjusted and repeated with additional adjustment for comorbidity, smoking, and alcohol consumption. After a median follow-up of 18.4years, treatment with BEP and MTOL was associated with overall increased risk of neurotoxicity (odds ratio 2.4-4.7 depending on treatment intensity, P < 0.001) as well as subscales (peripheral neuropathy, ototoxicity, and dysfunction associated with neuropathy, all P < 0.001). Radiotherapy and surveillance were not associated with neurotoxicity. In patients treated with BEP, neurotoxicity was highly associated with all indicators of worse QoL outcomes (P-trend: 1.5 × 10-17 to 1.1 × 10-28) after almost 20years of follow-up. Treatment with BEP was associated with long-term neurotoxicity, which was highly associated with decreased QoL. Strategies to ameliorate or prevent neurotoxicity should be investigated. Treatment with chemotherapy for testicular cancer induces long-term neuro- and ototoxicity which may have severe influence on quality-of-life years after treatment cessation.

Probability of carcinogenesis due to involved field and involved site radiation therapy techniques for supra- and infradiaphragmatic Hodgkin’s disease

PurposeTo estimate the second cancer risk associated with Hodgkin Lymphoma (HL) radiotherapy at supradiaphragmatic or infradiaphragmatic region, using the involved field (IFRT) and the involved site radiotherapy (ISRT). Materials and methodsIFRT and ISRT treatment plans were created for twenty HL patients. Three dimensional plans (3DRT) were employed for all patients. The organ equivalent dose (OED) and lifetime attributable risk (LAR) for organs at risk were estimated with mechanistic, plateau and bell-shaped model. Estimated risk values were compared with nominal risk of unexposed population. ResultsFor supradiaphragmatic radiotherapy, the mean OED range was 0.63–8.53 Gy and 0.63–7.26 Gy for IFRT and ISRT, respectively. The corresponding range for infradiaphragmatic radiotherapy was 0.18–7.64 Gy and 0.80–4.95 Gy. The LAR for cancer induction in the partially in field organs at risk after IFRT was 0.5%–8.0% and 0.2%–9.3% at supradiaphragmatic and infradiaphragmatic regions, respectively. The corresponding risk after ISRT method was 0.5%–5.2% and 0.9%–6.0%. Estimated cancer risk for breast, lung, thyroid, colon and rectal with ISRT was found significantly reduced compared to IFRT. The risk of secondary malignancies for lung, mouth, pharynx, rectum and colon was assessed more than 1.2 times higher than nominal risk for IFRT. The respective risk using ISRT was above nominal only for pharyngeal cancer. ConclusionISRT compared with IFRT, results in decreased second cancer risk in most organs considered. Second cancer probability with IFRT was higher than the nominal risk for certain organs, while for ISRT remains higher only for pharyngeal cancer.

Physical long-term side-effects in young adult cancer survivors: germ cell tumors model.

After the important advances in the treatment of germ cell tumors (GCTs) leading to high cure rates, physical long-term side-effects represent an important cause of death in these young adult survivors. Highlighting these physical long-term side-effects, their monitoring and their prevention modalities is necessary for a better management of these cancer survivors. Impaired fertility, increased risk of developing a second cancer, cardiac, pulmonary, renal and neural toxicity, hearing and vision impairment are the major physical side-effects in young adult cancer survivors. Long-term cardiac toxicity, next to second malignancies, represents life-threatening conditions in testicular cancer survivors. The long-term nephrotoxity in testicular GCTs survivors is most frequently associated to the treatment either in those treated with cisplatin-based chemotherapy, mainly Bleomycine, Etoposide, Cisplatin, or those receiving infradiaphragmatic radiation therapy, whereas pulmonary toxicity is mainly attributed to bleomycin related toxicities. There are no clear and comprehensive data concerning the monitoring and prevention of long-term side-effects in testicular cancer survivors. Physical activity and interventions in modifiable cardiovascular risk factors and lifestyles may reduce the incidence of long-term side-effects in these cancer survivors.

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 22.9 years, 55 patients developed CRC. The standardized incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8–3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6–4.6). The highest (SIR: 6.5, 95%CI: 3.3–11.3) was seen for transverse colon cancer (15.0 (95%CI: 4.3–40.8) after inverted-Y irradiation). A prescribed cumulative procarbazine dose >4.2 g m−2 was associated with a 3.3-fold higher CRC risk (95%CI: 1.8–6.1) compared to treatment without procarbazine. Patients receiving >4.2 g m−2 procarbazine and infradiaphragmatic radiotherapy had a hazard ratio of 6.8 (95%CI: 3.0–15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (Padditivity=0.004).Conclusions:Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy and a high cumulative procarbazine dose.

Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer: study design

BackgroundSecond primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer.Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach.We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires.Methods/DesignThis prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived ≥8 years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6–8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses.DiscussionEvaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors.Trial registrationRegistered at the Dutch Trial Registry (NTR): NTR4961.

P30. Experience feedback of a radiation protection incident in radiotherapy: Irradiation of a pregnant patient

Introduction A woman, treated by radiotherapy in the Centre Francois Baclesse in Caen for a head and neck cancer was proving pregnant (3rd month of pregnancy during the treatment).The pregnancy was revealed after the completion of the treatment (30 fractions – 2 Gy / fraction).In order to know the dose received by the fetus, measurements have been achieved with identical conditions as for the treatment. Materials and methods Irradiation technique:VMAT on a Clinac iX (Varian) linac.2 arcs of 307 UM and 278 UM with 6 MV photons.Phantom:Compact polystyrene to simulate the body and head and neck cylindrical phantom to simulate the irradiated volume.The ionization chamber was positioned at 45 cm of the field edge.This distance was measured by the medical doctor on the patient.The measurements were achieved with the same parameters recorded on the ”record and verify” software (Mosaiq – Elekta).The measurement cumulated 5 repetitions to improve the accuracy. Results For 1 fraction:0.83 mGy For the whole treatment (30 fractions):24.9 mGy Discussion 1/The dose far from the irradiation field has 3 components [1] -Photons scattered by the irradiated volume of the patient (internal) -Photons scattered by the irradiated materials (couch) and the walls of the treatment vault -Leakage radiation from the linac 2/The 1st component of the dose (scattered photons inside the patient) is very low because of the large distance between the field edge and the measuring point.In the ICRP report #84 (Pregnancy and medical radiation) [2] off axis values of dose are given for cobalt 60:approximately 0.25% at 45 cm but for linacs this off axis dose is lower 2–5 times (depending on beam energy).Our measurements (0.04%) are so, in good agreement with the ICRP #84 data.In the literature, several authors reported equivalent fetal doses for head and neck irradiations [3] [4] [7] .For irradiated volumes closer to the uterus (Hodgkin desease), the doses are obviously much greater [5] [6] . Conclusion The value of the effective dose measured ( ≈ 25 mSv) is superior to the upper legal limit for the fetus (1 mSv). In consequence, this case was declared as an incident to the French Nuclear Safety Authority (ASN) but it is assumed not to be critical for the children: – Malformations have a threshold of 100–200 mGy or higher and are typically associated with central nervous system problems [1] – A fetal dose of 100 mGy has a small individual risk of radiation-induced cancer. There is over a 99% chance that the exposed fetus will NOT develop childhood cancer or leukaemia [2]

Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment

ObjectiveHodgkin's lymphoma survivors who were treated with infradiaphragmatic radiotherapy or procarbazine-containing chemotherapy have a fivefold increased risk of developing colorectal cancer (CRC). This study aims to provide insight into the...

Testosterone deficiency in testicular cancer survivors - a systematic review and meta-analysis.

Results concerning treatment of Testicular Germ Cell Cancer (TGCC) and subsequent risk of testosterone deficiency are conflicting. To systematically evaluate and estimate the risk of testosterone deficiency (TD) in TGCC-patients according to treatment to optimize follow-up and for prevention of late effects related to hypogonadism. We performed a critical review of PubMed in January 2015 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Twelve publications were selected for inclusion in this analysis. Eleven studies evaluated the risk of TD in TGCC-patients treated with standard chemotherapy (CT) and the odds ratio for TD was 1.8 (95% CI) (1.3-2.5), (p=0.0007). Seven studies evaluated the risk of TD in TGCC-patients treated with non-conventional therapy and the odds ratio for TD was 3.1 (95% CI) (2.0-4.8), (p<0.0001). Six studies evaluated the risk of TD in TGCC-patients treated with infradiaphragmatic radiotherapy (RT), and the odds ratio for TD was 1.6 (95% CI) (1.0-2.4), (p=0.03). In all treatment groups the risk of TD was compared with TGCC-patients treated with orchiectomy alone. There was no indication of heterogeneity between studies in the three treatment groups. Strong evidence exists that standard CT, non-conventional therapy and infradiaphragmatic RT are associated with an increased risk of TD in TGCC-patients when compared with orchiectomy alone. The risk of testosterone defficiency appears to be highest in patients treated with non-conventional therapy.

Diabetes and the blood – white cells and platelets

Diabetes and the blood – white cells and platelets

Orchiectomy and radiotherapy for stage I-II testicular seminoma: a prospective evaluation of short-term effects on body image and sexual function.

Orchiectomy followed by infradiaphragmatic radiotherapy is a common treatment for stage I-II testicular seminoma. Long-term effects of orchiectomy and radiotherapy for testicular seminomas on body image and sexual function have been reported; however, few data are available on short-term effects. Patients are usually of reproductive age and sexually active; therefore, short-term effects on body image and sexual function should also be studied. To prospectively evaluate short-term effects of orchiectomy and radiotherapy on body image and sexual function in testicular seminoma patients. Questionnaires on body image and sexual function were prospectively distributed to all testicular seminoma patients treated between 1999 and 2013. The questionnaire distributed prior to radiotherapy was returned by 161 patients; 133 (82%) returned the second after 3 months, and 120 (75%) completed the questionnaire after 6 months. Body image and sexual function as assessed by a Dutch questionnaire on body image and sexuality after radiotherapy and orchiectomy. Median age was 36 years (range 18-70). After orchiectomy, 48% expressed fertility concerns, and 61% reported their body had changed. Six months after treatment, erectile rigidity was significantly decreased compared with prior to radiotherapy (P = 0.016), and 23% reported decreased sexual interest, activity, and pleasure. Changes in body image were significantly associated with decreased sexual interest, pleasure, and erectile function. Even though 45% reported that treatment negatively affected their sexual life, the number of sexually active patients remained stable at 91%. [Correction added on 12 November 2014, after first online publication: 'prior radiotherapy' was corrected to 'prior to radiotherapy'.] Short-term effects of treatment included fertility concerns and changes in body image. Reported erectile rigidity was significantly decreased after 6 months, as were sexual interest, activity, and pleasure. Disease and treatment had negative effects on sexual life, and changes in body image were associated with sexual dysfunction. Therefore, body image and sexual functioning should be addressed at an early stage in order to offer adequate treatment and counseling.

Risk of diabetes mellitus in long-term survivors of Hodgkin lymphoma.

Recently, an increased risk of diabetes mellitus (DM) was observed after abdominal irradiation for childhood cancer. Because many Hodgkin lymphoma (HL) survivors have also been treated with infradiaphragmatic radiotherapy, we evaluated the association between HL treatment and DM risk. Our study cohort comprised 2,264 5-year HL survivors, diagnosed before age 51 years and treated between 1965 and 1995. Treatment and follow-up information was collected from medical records and general practitioners. Radiation dosimetry was performed to estimate radiation dose to the pancreas. Cumulative incidence of DM was estimated, and risk factors for DM were evaluated by using Cox regression. After a median follow-up of 21.5 years, 157 patients developed DM. Overall cumulative incidence of DM after 30 years was 8.3% (95% CI, 6.9% to 9.8%). After para-aortic radiation with ≥ 36 Gy, the 30-year cumulative incidence of DM was 14.2% (95% CI, 10.7% to 18.3%). Irradiation with ≥ 36 Gy to the para-aortic lymph nodes and spleen was associated with a 2.30-fold increased risk of DM (95% CI, 1.54- to 3.44-fold) whereas para-aortic radiation alone with ≥ 36 Gy was associated with a 1.82-fold increased risk (95% CI, 1.02- to 3.25-fold). Lower doses (10 to 35 Gy) did not significantly increase risk of DM. The risk of DM significantly increased with higher mean radiation doses to the pancreatic tail (P < .001). Radiation to the para-aortic lymph nodes increases the risk of developing DM in 5-year HL survivors. Screening for DM should be considered in follow-up guidelines for HL survivors, and treating physicians should be alert to this increased risk.

Long-term outcomes of radiotherapy for stage II testicular seminoma–the Mayo Clinic experience

ObjectivesTo report long-term outcomes of patients with stage II testicular seminoma treated with radiotherapy (RT). Materials and methodsA retrospective review was performed of 52 patients who received megavoltage RT for stage II testicular seminoma at Mayo Clinic between 1974 and 2007. Forty-eight patients (92%) had computed tomography staging. Overall survival (OS), relapse-free survival (RFS), and cause-specific survival (CSS) were determined using the Kaplan-Meier method. Major cardiac event (MCE) was defined as myocardial infarction, coronary artery bypass grafting or stenting, or valve replacement. Second malignancy (SM) was defined as biopsy-confirmed malignancy occurring in the RT field. ResultsThe median patient age at diagnosis was 36 years. Stage was IIA (n = 24), IIB (n = 7), IIC (n = 17), and II not otherwise specified (NOS, n = 4). The median infradiaphragmatic RT dose was 30.7 Gy. Twenty-six patients (50%) received prophylactic mediastinal/supraclavicular (MSCV) RT. The median follow-up was 19 years. Estimates of OS, RFS, and CSS were 94%, 80%, and 96% at 10 years, and 83%, 72%, and 96% at 20 years, respectively. RFS at 10 years for stage IIA, IIB, IIC, and II NOS were 83%, 54%, 81%, and 100%, respectively (log-rank P = 0.21). Ten patients (19%) experienced disease relapse in the MSCV region (n = 7), para-aortic lymph nodes (n = 1), lung (n = 1), or peritoneal cavity (n = 1). Eight patients were successfully salvaged with chemotherapy and/or surgery, while 2 died of seminoma. Risk of MSCV relapse was significantly lower in patients who received MSCV RT vs. those who did not (10-year estimates: 4% vs. 21%, respectively, log-rank P = 0.01). MCE occurred in 10 patients (19%) at a median of 18 years (range 7–30) after RT. SM occurred in 5 patients (10%) at a median of 27 years (range 20–34) after RT. ConclusionsIn patients with stage II testicular seminoma treated with RT, relapse in the irradiated site was uncommon. Infradiaphragmatic RT alone was associated with a significant risk of MSCV failure. Most MCE and SM events occurred more than 20 years after RT, highlighting the importance of vigilant long-term follow-up.

Impact of Different Treatment Approaches on Pregnancy Outcomes in 99 Women Treated for Hodgkin Lymphoma

The aim of this study was to evaluate the pregnancy outcomes in women with Hodgkin lymphoma (HL) diagnosis, treated between 1972 and 1999 at Department of Radiotherapy and Hematology of University "Sapienza" of Roma. We retrospectively studied 99 female patients that conceived after treatment for HL. Fifty-nine (59%) were treated with chemotherapy and radiotherapy, 32 (32%) with radiotherapy alone as supradiaphragmatic or as infradiaphragmatic and 8 (8%) patients with chemotherapy alone. Ninety-nine patients reported 145 pregnancies. We observed 132 deliveries (2 of them twin births) after a median of 55 months (range, 14-278 months) from the end of therapy. Twelve women (12%) experienced 13 miscarriages after a median of 50 months (range, 13-120) from the end of therapy. We recorded 9/132 (7%) premature births and 3/134 babies (2%) were underweight at the time of birth. We recorded 2 cases of congenital malformations. No statistical differences were recorded when adverse pregnancy outcomes were analyzed with respect to chemotherapy alone, radiotherapy alone, or combined therapy. No significant associations between pregnancy outcomes and therapeutic approaches were found. In particular, the infradiaphragmatic radiotherapy showed no statistical association with miscarriages, premature birth, and low birth weight at term when compared with other therapeutic approaches.

Long-term outcomes of radiotherapy for stage II testicular seminoma: The Mayo Clinic experience.

327 Background: To report long-term outcomes of patients (pts) treated with radiotherapy (RT) for stage II testicular seminoma. Methods: Between 1974 and 2007, 52 pts received RT for clinical stage II testicular seminoma after radical inguinal orchiectomy; 3 pts were excluded due to no clinical follow-up. CT staging was used for 46 pts (94%). Estimates of overall (OS), relapse-free (RFS), and cause-specific (CSS) survival were determined using the Kaplan-Meier technique. Major cardiac event (MCE) was defined as myocardial infarction, coronary artery bypass grafting or stenting, or valve replacement. Second malignancy (SM) was defined as biopsy-confirmed malignancy occurring in the RT field. Results: The median pt age was 35 years. AJCC stage was IIA (n=23), IIB (n=7), IIC (n=15), and unknown (n=4). Three pts were treated for paraortic recurrence during surveillance for stage I seminoma. Four pts with IIB (n=1) or IIC (n=3) disease were treated with chemotherapy in addition to RT. The median total RT dose was 30.4 Gy. Prophylactic mediastinal/supraclavicular (MSCV) RT was given to 24 pts (49%). The median follow-up was 18 years (range 0.4-37). Estimates of OS, RFS, and CSS at 10 and 20 years were 94% and 81%, 79% and 70%, and 96% and 96%, respectively. OS, RFS, and CSS were not significantly different between stage groups. Recurrence occurred in 9 pts (18%); sites were MSCV (n=6), para-aortic (n=1), lung (n=1), and peritoneal cavity (n=1). Seven pts were successfully salvaged, while 2 pts died of seminoma. No patient with stage IIA/B that received prophylactic MSCV RT (n=11) experienced MSCV relapse. Among patients that did not receive prophylactic MSCV RT, 2 of 13 (15%) with stage IIA and 3 of 6 (50%) with stage IIB experienced MSCV relapse. MCE occurred in 10 pts (20%) at a median of 18 years (range 7-30) after RT. SM occurred in 5 pts (10%) at a median of 27 years (range 20-34) after RT. Conclusions: Infradiaphragmatic RT alone was associated with a significant risk of MSCV failure, particularly in patients with stage IIB disease, suggesting that chemotherapy may be the optimal treatment in this patient cohort. Most MCE and SM events occurred more than 20 years after RT, highlighting the importance of vigilant long-term follow-up.

Stage I Seminoma: Adjuvant Treatment is Effective but is it Necessary?

Stage I Seminoma: Adjuvant Treatment is Effective but is it Necessary?

Risk of second cancers among a cohort of 2,703 long-term survivors of testicular seminoma treated with radiotherapy.

4538 Background: Stage 1 testicular seminoma has been treated by only orchidectomy and adjuvant infradiaphragmatic radiotherapy for the last half-century, occurs in early adult life and has an excellent prognosis, thus permitting the analysis of radiation carcinogenesis. Methods: A cohort of 2703 survivors of stage 1 seminoma treated with infradiaphragmatic radiotherapy from the UK and Norway were identified from radiotherapy center records and then matched to individual national cancer registry data to determine incidence of subsequent cancers. The identification of subjects from treatment records enabled investigation of dose and field size effects with more precision than previous epidemiological studies based on cancer registry data alone. The primary endpoint was number of non-testis second cancers (excluding non-melanoma skin cancers). Specific second cancers were analysed of sites related to the standard radiotherapy field. Person years of observation (PY) were compiled by age and calendar periods from 3 months after the end of radiotherapy to date of diagnosis of second cancer. Patients were censored at death or at 31/12/2005 (Norwegian patients) or 31/12/2007 ( UK patients). Cancer incidence rates specific for country, age, sex, and 5-year calendar period were used to determine expected number of cancers and standardised incidence ratios (SIR) based on assumption of a Poisson distribution. SIRs were analysed with respect to RT parameters i.e. dose, field and machine type. Results: Median follow up was 18.0 years (IQR 8.6-23.7 years); total PYs at risk was > 53,600 during which 385 second cancers were reported in 354 men. The excess of second cancers in long-term survivors was statistically significant (SIR 1.31; 95% CI 1.19-1.45). Sites with statistically significant excess risk were stomach (SIR 1.63; 95% CI 1.08-2.45), pancreas (SIR 2.35; 95%CI 1.52-3.64) and bladder (SIR; 2.14 95%CI 1.58-2.88). Conclusions: Infradiaphragmatic radiotherapy is associated with a significant excess of second cancers; policies for treating stage 1 seminoma should be revised. No significant financial relationships to disclose.

Male reproductive potential after MOPP therapy for Hodgkin's disease: a long-term survey.

The testicular function of 47 men who had been treated by MOPP chemotherapy for a Hodgkin's disease was studied in a long-term survey. Azoospermia was constant during at least 14 months after completion of the treatment. After a follow-up period of 89.4 +/- 54.7 months, 26 men were still azoospermic. No correlation could be found between the therapeutic regimen and the results of semen analysis. For the same treatment, some men recovered spermatogenesis within 5 years, others after more than 10 years while some were still azoospermic after 20 years. However, the association of infra-diaphragmatic irradiation to high dose MOPP therapy had a profound detrimental effect on spermatogenesis: only 3/13 men recovered. Sperm recovery was often incomplete: 17/21 men had a sperm count below 20 million ml-1. Yet, spontaneous pregnancies were obtained with severe oligozoospermia: only 1/11 sperm counts performed close to fertilization exceeded 20 million ml-1, and 8 were below 5 millions ml-1. FSH failed to be either a sensitive or a specific marker of sperm recovery, a discrepancy between FSH level and spermiogram being noticed in 18.2% of cases.