Risk of subsequent cancer following a primary CNS tumor

Improvements in survival among central nervous system (CNS) tumor patients has made the risk of developing a subsequent cancer an important survivorship issue. Such a risk is likely influenced by histological and treatment differences between CNS tumors. De-identified data for 41,159 patients with a primary CNS tumor diagnosis from 9 Surveillance, Epidemiology and End Results (SEER) registries were used to calculate potential risk for subsequent cancer development. Relative risk (RR) and 95 % confidence interval (CI) of subsequent cancer was calculated using SEER*Stat 7.0.9, comparing observed number of subsequent cancers versus expected in the general United States population. For all CNS tumors studied, there were 830 subsequent cancers with a RR of 1.26 (95 % CI, 1.18–1.35). Subsequent cancers were observed in the CNS, digestive system, bones/joints, soft tissue, thyroid and leukemia. Radiotherapy was associated with an elevated risk, particularly in patients diagnosed with a medulloblastoma/primitive neuroectodermal tumor (MPNET). MPNET patients who received radiotherapy were at a significant risk for development of cancers of the digestive system, leukemia, bone/joint and cranial nerves. Glioblastoma multiforme patients who received radiotherapy were at lower risks for female breast and prostate cancers, though at an elevated risk for cancers of the thyroid and brain. Radiotherapy is associated with subsequent cancer development, particularly for sites within the field of radiation, though host susceptibility and post-treatment status underlie this risk. Variation in subsequent cancer risk among different CNS tumor histological subtypes indicate a complex interplay between risk factors in subsequent cancer development.     

A retrospective cohort analysis of second breast cancer risk for primary breast cancer patients with an assessment of the effect of radiation therapy

Second breast cancer experience was examined for 27,175 primary breast cancer patients diagnosed in the State of Connecticut during 1935-75 with follow-up for second breast cancers through 1980. The overall ratio of observed to expected second breast cancers was 3.2. Relative risk was found to be inversely related to age at diagnosis and directly related to stage of the first breast cancer. The overall risk of second breast cancers was 711 per 100,000 person-years at risk. Risk of second breast cancers showed a similar relationship to age and stage as relative risk and was also directly related to calendar period of diagnosis of the first breast cancer. Some interactions were observed because patients less than 45 years old at diagnosis with positive nodes had elevated risks and relative risks in the early followup period, whereas less of an effect of stage on relative risk and risk was seen for older patients. The effect of the use of adjunctive radiation therapy on second breast cancer risk was also assessed by the ratio of the risk of second breast cancers for those patients who received both surgery and radiation to the risk of those patients who only received surgery being estimated for patients diagnosed during 1935-59 and for patients diagnosed during 1960-75. For both cohorts relative risks of 1.2-1.4 were found for the 5-year period immediately following diagnosis, likely resulting from the uncontrolled effect of stage in the analysis. Elevated long-term relative risks were not found for patients diagnosed during 1935-59. A long-term marginally statistically significant relative risk of 1.4 (greater than or equal to 10 yr after diagnosis) was found for patients diagnosed during 1960-75. The data do not indicate an overall pattern of relative risks consistent with an effect on long-term second breast cancer risk of radiation exposure to the opposite breast incurred during adjunctive radiation therapy for a first breast cancer.     

Second cancers following antineoplastic therapy

The occurrence of metachronous malignancies has long been a phenomenon of interest to physicians. The problem of treatment-related malignancies has added to that interest and has contributed to the understanding of carcinogenesis. Prolonged survival of patients with previously lethal diseases is now allowing the expression of long-term toxicities of the intensive therapies being used in many disease settings. Although the oncogenic potential of the various alkylating agents may not be equivalent, they have all been implicated as causing cancer in man. Procarbazine also appears to be highly carcinogenic in man. The intensity of treatment (duration and total dose) is a significant factor in the carcinogenesis of these agents. The dose-response relationship between radiation and cancer induction is less clear, but most believe that increasing radiation exposure increases the risk of cancer in a linear fashion. The combination of intensive chemotherapy and intensive radiotherapy yields the greatest risk for treatment-related hematologic and solid malignancies. To replace effective therapy with less carcinogenic therapy of unproved effectiveness would be difficult since survival curves have not been significantly affected by the evolution of treatment-related cancers. Whether that will hold true for the adjuvant use of intensive therapy remains to be seen. Where feasible, the design of such adjuvant trials should keep the dose-response relationship in mind. If the virtual absence of metachronous leukemia in Hodgkin's disease patients treated with ABVD holds true over time, the search for noncarcinogenic combination therapy will be well worth the effort. Therapeutic options in cancer treatment currently are few, and the benefits of potentially carcinogenic chemotherapy and radiotherapy continue to outweigh the risks.     

Thyroid cancer and multiple primary tumors in the SEER cancer registries

Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End-Results (SEER) cancer registries program (1973-2000). In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) = 35-50%; excess absolute risk (EAR) = 0.38/10,000 person-years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/expected (O/E) = 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2-month thyroid cancer survivors, 2,214 second cancers occurred (O/E = 1.11, 95% CI = 1.06-1.15; EAR = 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E = 1.26). Patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment-related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking-related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2-way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects.     

Atypical teratoid/rhabdoid tumor: the controversy behind radiation therapy

To date, approximately 200 cases of atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system have been described in the literature. This CNS tumor tends to present at an age of less than 3 years, and most patients succumb to their disease within 1 year of diagnosis. Prior to the rise in utilization of immunohistochemical (IHC) testing in the late 1990s, this tumor was likely mistaken as medulloblastoma and treated as such. However, lessons learned from regimens based upon medulloblastoma have revealed that AT/RT requires more aggressive treatment. A significant portion of patients die of local recurrence in spite of aggressive surgery and chemotherapy. As most patients with AT/RT present as infants or young children, radiation therapy has been a less than standard treatment option. However, recent evidence suggests that long-term survival can occur with use of more aggressive treatment approaches including dose-intense chemotherapy as well as adjuvant radiation therapy. A standardized and effective approach to treating this usually fatal tumor remains elusive, and the role of radiation therapy presents a particular dilemma as young patients with this disease may experience devastating late effects of therapy if they achieve a long-term survival. Review of the literature reveals an association between initial radiation therapy and the ability to achieve a prolonged survival. Our review underscores the importance or enrolling patients in multi-institutional prospective studies to further investigate the value of radiation to treat this pediatric neoplasm.     

Medulloblastoma: clinical and biologic aspects

Medulloblastoma is the most common childhood primary CNS tumor, and treatment approaches have evolved over the past three decades. The biologic underpinnings of medulloblastoma are not fully characterized, but recent work has identified new, important directions for research. Stratification of patients with medulloblastoma into risk groups is the backbone of most ongoing therapeutic studies. Patients are usually characterized as being either average risk or poor risk, although an intermediate risk group may exist. Standard treatment for older children with medulloblastoma consists of radiation and, for most, chemotherapy. Children with nondisseminated disease at the time of diagnosis have been reported to have as high as an 80% five-year disease-free survival rate after treatment with reduced dose (2340 cGy) craniospinal irradiation, local boost radiation therapy (5500 cGy), and chemotherapy, given during and after radiation therapy. Preradiation chemotherapy has yet to be shown to be of benefit for children with medulloblastoma. Children with disseminated disease are a highly problematic subgroup of patients to treat. A variety of new approaches are being studied, most of which are intensifying chemotherapy either prior to or after radiation. Long-term survivors of medulloblastoma are at significant risk for permanent endocrinologic, cognitive, and psychological sequelae. Infants and very young children with medulloblastoma remain a difficult therapeutic challenge because they have the most virulent form of the disease and are at highest risk for treatment-related sequelae.     

A note from history: Landmarks in history of cancer,part 5

In the 3 decades from 1910 to 1940, more progress took place in cancer research and the diagnosis and treatment of cancers than during the prior centuries combined. The discovery of several carcinogens, precancerous conditions, and hereditary cancers adduced new thoughts about the genesis of cancers. Even though diagnostic radiology and radiation therapy became apposite specialties, surgery retained its primacy in the treatment of cancer patients. The delineation of new and distinct neoplastic entities, several precancerous lesions, and noninvasive carcinomas as well as the introduction of histopathologic grading of cancers promulgated cogent changes in therapy. Yet, with all the advances in the diagnosis and treatment of cancers, very little betterment could be demonstrated in the overall survival of patients, and by the end of the 1930s, cancer became the second most common cause of death in the United States. Cancer 2013. © 2012 American Cancer Society.     

Radiation-induced cancer as a factor in clinical decision making (the 1989 ASTRO Gold Medal address)

1. Ionizing radiations are weak carcinogens. Under certain conditions they can induce cancers in experimental animals and humans. 2. This potential carcinogenicity has been a deterrent to the use of radiation therapy despite its many advantages in the management of patients with cancers. 3. In a range of clinical situations, such as the irradiation of cancers arising in the head and neck, breast, prostate and skin, an increase of second cancers can not be detected above the natural frequency of additional cancers. In the curative treatment of patients with Hodgkins disease, ionizing radiations are not associated with an increased frequency of leukemias and induced second tumors are no more frequent than following the use of alkylating agents. 4. All second tumors attributed to radiation therapy occur after a latent period of many years and except for leukemia usually are potentially curable. 5. The risks of radiation-induced second cancers are no greater than the risks of operative or anesthetic deaths and these catastrophes are immediate and non-remedial. 6. Therefore, at this time, the potential of radiation-induced cancers should not be a factor in the selection of treatment for patients with cancer.     

Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers

Although radiation is considered a risk factor for thyroid cancer, the potential relationship between radiation therapy and the risk of second primary cancer among patients with first primary thyroid cancer has not been evaluated. We identified 26,639 patients with first primary thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2000. Information on radiation therapy as well as second primary cancers was recorded in SEER. The proportional hazards model was utilized to estimate adjusted risk ratios (RRs) and their 95% confidence intervals (CIs) to assess the potential association between radiation therapy for thyroid cancer and the risk of second primary cancers. With 270,674.33 person-years of follow-up, 1,896 (7.1%) of the 26,639 patients with first primary thyroid cancer developed second primary cancers. Among the second primaries, 35 occurred in the thyroid. No obvious association was observed between radiation therapy and the overall risk of second primary cancer after ten years of follow-up (RR=1.07, 95% CI=0.88-1.30). However, an increased risk was seen for several cancers, including upper digestive system cancers (RR=1.66, 95% CI=1.07-2.57) and myeloid malignancies (RR=3.26, 95% CI=1.39-7.67). Radiation therapy was associated with reduced second cancer risks for thyroid cancer (RR=0.18, 95% CI=0.04-0.76). Beam radiation might be important to the digestive system, radioactive implants might be associated with the male genital system, radioisotopes might have an effect on myeloid malignancies, and combined beam radiation with radioactive implants or radioisotopes might be related to the increased risk of respiratory system cancers. This study suggests that radiation therapy for patients with first primary thyroid cancer might be associated with an increased risk of developing a second primary cancer in the upper digestive system and second primary myeloid malignancies. Radiation therapy for adult patients with thyroid cancer might be associated with a reduced risk of second primary thyroid cancer.     

Radiotherapy in the treatment of hereditary breast cancer

Hereditary breast cancer represents approximately 5% to 10% of breast cancers and a larger portion of patients with early-onset disease. Given the relatively recent identification of the BRCA1 and BRCA2 genes, the available literature with respect to outcomes related to radiation therapy has inherent limitations with relatively small patient numbers and a lack of prospective randomized trials. There is, however, a growing body of literature describing treatment and toxicity outcomes in patients undergoing radiation therapy after breast-conserving surgery and after mastectomy for breast cancer patients who have BRCA1 and BRCA2 mutations. Acknowledging the limitations in the available data, there does not appear to be any evidence of more severe normal tissue reactions or compromised long-term survival rates in women electing breast-conserving surgery and radiation. These studies are reviewed in this article. Outcomes related to radiation therapy in patients with variants in other breast cancer-related genes, such as p53, ATM, CHEK2, PALB2, and PTEN, are even less well documented because of the paucity of data. Available reports on radiation-related outcomes in these and single nucleotide polymorphisms in radiation repair and response genes are discussed.     

Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: A Children's Cancer Group Study.

PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% +/- 4% at 3 years and 79% +/- 7% at 5 years. Sites of relapse for the 14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma.     

Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases

BACKGROUND: The purpose of the current study was to characterize the outcomes of patients with metastatic triple-negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence. METHODS: Using pharmacy and pathology records, a study group of 116 patients who were treated for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute between January 2000 and June 2006 was identified. RESULTS: The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases before death. The median survival after a diagnosis of CNS metastasis was 4.9 months. The age-adjusted and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95% confidence interval, 1.9-6.1 times) that of patients without a CNS lesion at the time of first metastatic presentation. Of the 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow-up before death. CONCLUSIONS: Triple-negative breast cancer is associated with poor survival after recurrence. CNS recurrence is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is because of a sanctuary effect, but rather is due to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed.     

Survival of breast cancer patients with synchronous or metachronous central nervous system metastases

BackgroundCentral nervous system (CNS) metastases represent a devastating complication for advanced breast cancer patients. This observational study examines the influence of patient, tumour and treatment characteristics on overall survival after synchronous or metachronous CNS metastases.MethodsInformation on 992 breast cancer patients with CNS metastases (whose primary tumour was diagnosed between 2004 and 2010) was retrieved from the Netherlands Cancer Registry (NCR). Overall survival was calculated from the date of CNS metastatic diagnosis, and the impact of prognostic factors on survival was assessed using univariate and multivariate extended Cox-regression models.ResultsWe identified 165 patients with synchronous and 827 patients with metachronous CNS metastases. The majority of patients (88%) presented with brain metastases only, 12% had leptomeningeal metastases. Overall median survival was 5.0 months. Non-triple-negative breast cancer and systemic therapy were associated with improved survival in both groups. In patients with synchronous CNS metastases, surgery for the primary tumour and the metastases also improved survival. In patients with metachronous metastases, younger age (<50 years), lower initial tumour stage (I), ductal carcinoma, a prolonged time interval until diagnosis of CNS metastasis (>1 year), and absence of extracranial metastases were associated with improved survival. Metastasectomy and radiation therapy did not provide benefit beyond the first six months.ConclusionsNo difference in survival was established between synchronous and metachronous CNS metastases. Triple-negative disease is prognostically unfavourable in both groups, while those receiving treatment have a better outcome. Metastasectomy and radiotherapy improve survival within the first six months, and additional benefit may be derived from systemic therapy.     

Re-irradiation for Paediatric Tumours

Despite best available therapy, many children with cancer develop recurrence after multimodal treatment, including initial radiation therapy. Re-irradiation is defined as the use of a second course of radiation therapy with a retreatment volume that overlaps substantially with that of a previously delivered course of radiation therapy. Re-irradiation is an important part of salvage treatment for patients with recurrent ependymoma, diffuse intrinsic pontine glioma, medulloblastoma and germinoma. In patients with ependymoma, conventionally fractionated re-irradiation (1.8 Gy/day) can provide long-term disease control with low rates of high-grade toxicity. For children with progressive diffuse intrinsic pontine glioma, re-irradiation provides effective palliation of symptoms and a survival gain as compared with those treated without re-irradiation. Repeat radiation therapy that includes craniospinal irradiation, if safe to deliver, may provide long-term tumour control in patients with medulloblastoma. Patients with recurrent intracranial germinoma can be effectively salvaged with re-irradiation that includes craniospinal irradiation. Finally, the emerging role of re-irradiation in non-brainstem high-grade glioma and extracranial solid tumours requires further study regarding its efficacy and safety. When given, re-irradiation should be delivered with care so that doses to organs at risk are minimised. In all cases, re-irradiation should be considered as an option alongside, or concurrently with, other salvage treatments, including surgery or systemic therapy, to maximise the likelihood of durable disease control.     

Radiation-induced malignancies following radiotherapy for breast cancer

With advances in diagnosis and treatment, breast cancer is becoming an increasingly survivable disease resulting in a large population of long-term survivors. Factors affecting the quality of life of such patients include the consequences of breast cancer treatment, which may have involved radiotherapy. In this study, we compare the incidence of second primary cancers in women who received breast radiotherapy with that in those who did not (non-radiotherapy). All women studied received surgery for their first breast cancer. Second cancers of the lung, colon, oesophagus and thyroid gland, malignant melanomas, myeloid leukaemias and second primary breast cancers were studied. Comparing radiotherapy and non-radiotherapy cohorts, elevated relative risks (RR) were observed for lung cancer at 10-14 years and 15 or more (15+) years after initial breast cancer diagnosis (RR 1.62, 95% confidence interval [CI] 1.05-2.54 and RR 1.49, 95% CI 1.05-2.14, respectively), and for myeloid leukaemia at 1-5 years (RR 2.99, 95% CI 1.13-9.33), for second breast cancer at 5-10 years (RR 1.34, 95% CI 1.10-1.63) and 15+ years (RR 1.26, 95% CI 1.00-1.59) and oesophageal cancer at 15+ years (RR 2.19, 95% CI 1.10-4.62).     

Preradiation chemotherapy for newly diagnosed childhood brain tumors. A modified Phase II trial

A poor-risk population of children with primary malignant central nervous system (CNS) tumors, other than gliomas, can be identified by their young age, by the presence of disease dissemination at diagnosis, and possibly by subtotal resection of the primary tumor. These children require at least neuraxis radiation therapy and possibly chemotherapy for disease control. Unfortunately, once neuraxis radiation is administered, tolerance of subsequent chemotherapy is limited. The authors have explored a multimodal treatment approach in 14 poor-risk patients initially consisting of a modified Phase II chemotherapy trial followed by neuraxis radiation. The diagnoses were medulloblastoma (5), pineoblastoma (3), cerebral primitive neuroectodermal tumor (3), germinoma (2), and choroid plexus carcinoma (1). Eleven patients had disseminated CNS disease, and two had bone marrow involvement at diagnosis. Nine patients received 2 courses of intravenous cyclophosphamide (80 mg/kg) alone over 8 weeks, and five others received three daily doses of intrathecal Ara-C (50 mg/m2) and oral hydroxyurea (40 mg/kg) with each course of cyclophosphamide. There were four complete responses (two dysgerminomas, one pineoblastoma, and one primitive neuroectodermal tumor), one partial response (medulloblastoma), and three mixed responses (two medulloblastomas, one pineoblastoma) to chemotherapy alone, for a response rate of 57%. Twelve patients subsequently tolerated the planned dose of neuraxis radiation. The median survival of all patients was 11 months, and seven of eight deaths were related to recurrent disease. The hematologic toxicity was appreciable, and one death resulted from gram-negative septicemia. Through the use of this type of Phase II trial, valuable information can be obtained on the response rates to specific chemotherapy agents administered prior to radiation. Although cyclophosphamide alone was an active agent in this context, these treatment regimens did not have an important affect on survival.     

Current Therapeutic Options for Breast Cancer Central Nervous System Metastases

Opinion statement  Breast cancer metastases to the central nervous system (CNS) has devastating consequences for the individual. As treatment options for metastatic breast cancer expand and as quality of life and overall survival improve, researchers are targeting potential treatments for this sanctuary site. Attention is now being focused on defining the phenotype of breast cancer that has a propensity to metastasize to the CNS. Specific therapies that penetrate the blood brain barrier as well as adjuvant therapies that decrease recurrence in the CNS are currently being investigated. We will review current approaches to the diagnosis, evaluation, and treatment of CNS metastases in breast cancer patients.     

Carcinogenic effects of scattered dose associated with radiation therapy

Ionizing radiation has long been recognized as a weak carcinogen, and the risk of developing a radiation induced neoplasm after exposure to therapeutic radiation has been established. In the case of therapeutic radiation for treatment of existing malignancies, concomitant risk factors for second malignancies can confound the effect of radiation alone. This study presents a model for evaluating the isolated contribution of ionizing radiation to the induction of second malignancies in cancer patients, and presents estimates of the expected number of second malignancies induced in selected sensitive sites by scatter radiation during radiotherapy for cancer. The study focused on the year 1987, during which it was estimated that 192,761 new cancer patients received radiotherapy as part of their initial treatment plan. The model predicted that radiation may induce 63-84 secondary breast cancers, 64-72 secondary thyroid cancers, 94-157 secondary lung cancers, and 489-707 secondary leukemias over the remaining lifetime of this patient population. This represents a lifetime incidence of 0.7% for leukemia, and 0.3% for the solid tumors. This incidence must be placed in perspective with the current concepts of cancer management, such as combined modality therapy that may carry a risk of carcinogenesis greater than either modality alone, and when the alternatives to radiotherapy may be nonexistent or may be cosmetically or functionally undesirable. The information presented may be used in weighing the risks and benefits of alternative treatments for cancer.     

Second Primary Cancer after Diagnosis of Stomach Cancer in Osaka, Japan

The risk of developing a second primary cancer following stomach cancer was estimated from data accumulated in the Osaka Cancer Registry. Of the 38,777 male patients and 22,391 female patients newly diagnosed in the period 1966–1986 who were followed up until the end of 1986, 778 and 267 developed a second cancer other than stomach cancer, respectively, whereas the expected numbers had been 928.8 (RR=0.84, 95%CI=0.78-0.90) and 297.7 (RR = 0.90, 95%CI = 0.79-1.01). The risks were higher among younger patients (aged 30–54 at the diagnosis of stomach cancer) than among older patients (aged 55–69 at the diagnosis of stomach cancer). Significantly elevated risks were observed for cancers of the oral cavity & pharynx (RR=l.56), colon (RH = 1.61) and rectum (RR = 1.56) for males, and oral cavity & pharynx (RR = 2.59) for females as second cancers. Results were substantially similar among the localized stomach cancer patients. Among younger male patients with gastrectomy, the risk of developing pancreatic cancer was elevated 10 or more years after stomach cancer diagnosis. The present study suggests the necessity of following up stomach cancer patients in order to enable the early diagnosis of digestive tract cancer.     

Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I,Medically Inoperable Non–Small-Cell Lung Cancer – Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non–small-cell lung cancer (OCOG-LUSTRE Trial).Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery.Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks.