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Second cancer after radiation therapy for cancer of the uterine cervix.

Radiation-induced cancers after radiation therapy for cancer of the uterine cervix were investigated on 11,855 patients including 5725 patients treated with radiation therapy alone, 1969 postoperative radiation therapy and 4161 surgery alone. The observed-to-expected ratios of the second primary cancer was 0.933 for the patients with radiation therapy alone and 1.074 for the patients with postoperative radiation therapy, respectively. No significant increase was observed in the risk of second primary cancers when all sites were combined. However, assessing on site by site basis, significant excess was noted for the rectum cancer, leukemia, and bladder cancer for the radiation therapy group but not for the surgery group. A significant excess of lung cancer was observed in both radiation therapy and surgery groups, which was attributed to some other causative factors. Radiation-induced cancers were suggested to develop apparently in organs involved in the irradiated field.

Adult↗

Malignant glioma following radiotherapy for unrelated primary tumors.

Four cases are documented where a glioma was histologically verified in the irradiation field of a previously treated malignancy of a different cell line. Radiation-induced neoplasia in the central nervous system now has been established in the induction of meningioma and sarcoma. The association between therapeutic irradiation and glioma in the reported cases lends to the evidence that a causal relation does exist. This incidence is small and does not detract from the overall benefit of irradiation as a therapeutic modality.

Adult↗

A clinico-pathological study on the correlation of immunosuppression and multiple primary malignant neoplasmas.

At present it is obvious that the incidence of second malignancies in patients with malignant diseases increases after prolonged treatment with immunosuppressive, or antineoplastic agents. The occurrence of such additional malignant diseases was analysed in our five-years autopsy material. During this period 7670 autopsies were performed. Malignant diseases were observed in 1707 cases (22.1%) and among them in 58 cases were proved multiple primary malignant neoplasms (3.3%). The average time between the occurrence of initial and second tumors was 29 months. The frequency of second tumors in patients with leukemias (mainly chronic lymphocytic leukemia) were four times higher than in patients with tumors of epithelial origin. Hepatocarcinomas arose in cirrhotic livers and astrocytomas were often followed by new malignancies. In consequence of successfully applied surgical, radiological and combined immunosuppressive, antineoplastic therapy the survival of cancer patients lengthened, so among different side-effects of the used therapy the oncogenesis cannot be left out of account. The danger of subsequent malignant tumors makes it imperative that immunosuppression should only be applied when strictly indicated.

Adult↗

The results of modern surgical therapy for multiple primary lung cancers.

STUDY OBJECTIVES: The purpose of this report is to review our experience with multiple primary lung cancers (MPLC) at the Walter Reed Army Medical Center, Washington, DC, and to determine the outcome of our surgical management of this complex problem. PATIENTS AND METHODS: The data from the Lung Cancer Registry on patients with MPLC from January 1984 to December 1995 were reviewed. We used the criteria of Martini and Melamed modified by Antakli for the diagnosis of synchronous and metachronous MPLC. Survival probabilities were calculated by the Kaplan-Meier actuarial method with the dates of resection as the starting point and included deaths from all causes. The log rank test was used to compare survival rates between groups and Wilcoxon rank sum test was used to compare the intervals between the first and the second metachronous cancers. A p value of 0.05 was considered statistically significant. RESULTS: Fifty-two patients, consisting of 51 patients who had "curative" pulmonary resections and 1 patient who had radiation therapy for previous primary lung cancer, developed second or third primary lung cancers. Thirty-seven patients developed metachronous cancers within 1 to 15 years of the first operation (median, 24 months) while 15 patients had synchronous cancers (10 unilateral, 5 bilateral). The probability of cancer-free interval among patients with metachronous cancers was 41% at 3 years, 16% at 5 years, and 3% at 10 years. Two of the 36 patients who had pulmonary resection for the second metachronous cancer died in the perioperative period (operative mortality, 5.6%), and one patient had radiation therapy for the second metachronous cancer. There were no deaths among patients with synchronous cancers. The actuarial 5-year survival for second metachronous cancers was 37% and for synchronous cancers was 0%. CONCLUSIONS: We conclude that an aggressive surgical approach is safe and justified in most patients with MPLC, especially patients with metachronous cancers, while patients with synchronous lung cancers have poorer prognosis. The operative morbidity and mortality are acceptable and long-term survival is possible in many patients with metachronous lung cancer.

Actuarial Analysis↗

[A solitary cerebellar metastasis: a diagnostic exercise].

Presentation of a solitary cerebellar mass lead us to think about the presence of a primary tumour or the possibility of a pulmonary, mammary or digestive metastasis. However, once discarded these origins, is necessary to search the primary neoplasms in less frequent organs. Approximately, 5% of all intracranial metastasis have it's origin in a renal cancer. These lesions generally appear at the supratentorial area and within a generalized disease. In the other hand, the presentation of a solitary cerebellar metastasis from a renal carcinoma without affectation of other organs is a very unusual fact. We present a case of these characteristics discussing about diagnostic, therapeutic and prognostic aspects of this unpredictable tumor.

Adenocarcinoma, Clear Cell↗

Risk of radiation-related subsequent malignant tumors in survivors of Ewing's sarcoma.

Twenty-four long-term survivors of Ewing's sarcoma were identified as being at risk for a second primary tumor. Among this group of patients followed from 3 to 22 years, 4 new bone tumors were observed, whereas 1.2 x 10(-3) were expected. All new tumors arose in heavily irradiated areas. The risk associated with radiation after 3 years was 7.2 cases/million person-years per rad. The cumulative cancer risk over 10 years for irradiated patients was 35% (SE, 15.1%). Intensive chemotherapy (cyclophosphamide and vincristine administered in five or more courses) seemed to exert an enhancing effect, increasing the rate of development of new tumors.

Adolescent↗

Distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

BACKGROUND: In patients with head and neck squamous cell carcinoma (HNSCC), a squamous cell carcinoma (SCC) in the lung represents either another primary tumor or a metastasis. This distinction greatly influences patient prognosis and could guide treatment strategies, but the nature of a solitary lung nodule is often difficult to discern by use of standard clinical and histologic parameters. Comparison of genetic alterations in the tumors could resolve this dilemma. METHODS: We compared paired tumors from 16 patients with HNSCC and a solitary lung SCC for loss (i.e., deletion) of loci on chromosomal arms 3p and 9p. Losses at these loci occur early during neoplastic transformation of the respiratory tract. DNA from microdissected tumors and normal tissues was subjected to polymerase chain reaction-based microsatellite analysis. An effort was also made to distinguish primary lung cancers from lung metastases on the basis of clinical and histopathologic features. RESULTS: In most cases, comparison of genetic alterations clarified the relationship between the lung tumor and the primary HNSCC. The paired tumors from 10 patients had concordant patterns of loss at all loci suggesting metastatic spread, whereas three paired tumors had discordant patterns of loss at all loci suggesting independent tumor origin. These observations were supported by the clinical and pathologic findings. CONCLUSIONS/IMPLICATIONS: In patients with HNSCC and a solitary SCC in the lung, microsatellite analysis provides a rapid genetic approach for discerning clonal relationships. In such patients, we found that a solitary SCC in the lung more likely represents a metastasis than an independent lung cancer. Microsatellite analysis could potentially be applied to any patient with multiple tumors, where tumor relationships are not clear on clinical, radiographic, or even histopathologic grounds.

Adult↗

Acute lymphoblastic leukemia followed by a clonally-unrelated EBV-positive non-Hodgkin lymphoma and a clonally-related myelomonocytic leukemia cutis.

BACKGROUND: Complicating malignant hematopoietic proliferations might severely hamper the course of acute lymphoblastic leukemia (ALL) in patients with an otherwise good prognosis. It is important to distinguish whether such neoplastic proliferations represent ALL relapses or secondary treatment-related malignancies. PROCEDURE: We present an 11-year-old girl with precursor-B-ALL in whom maintenance treatment was complicated by an isolated ALL relapse in the brain, nodular lymphoproliferations in the liver, and an isolated myelo-monocytic leukemia cutis. All these hemato-oncologic malignancies occurred in the background of a secondary immunodeficiency, most likely caused by cytotoxic treatment. RESULTS AND CONCLUSIONS: Using a stepwise molecular approach, we were able to demonstrate that the liver infiltrates were Epstein-Barr virus (EBV)-positive, contained monoclonal mature B-cells with immunoglobulin heavy chain gene (IGH) gene rearrangements unrelated to the primary ALL, and thus represented a true secondary non-Hodgkin lymphoma (NHL). In contrast, the skin infiltrates consisted of myelo-monocytic cells with clonal IGH and T-cell receptor gamma gene rearrangements, identical to the precursor-B-ALL blasts at diagnosis. Thus, the disease course of the precursor-B-ALL patient was complicated by two different isolated extramedullary relapses (brain and skin) and a secondary EBV(+) B-NHL.

Child↗

Highly aggressive policy of hepatic resections for neuroendocrine liver metastases.

BACKGROUND/AIMS: Neuroendocrine tumors are usually slow growing and carry a prolonged prognosis. The presence of liver metastases significantly impairs long-term survival. The clinical experience with 28 patients admitted since 1981 for liver metastases from neuroendocrine tumors was retrospectively reviewed to analyze the clinical and surgical management and to evaluate their outcome. METHODOLOGY: Surgery was indicated in 25 (89.2%) patients. Three had metachronous metastases. A correct diagnosis of these liver metastases was achieved before laparotomy in 15 (68.1%) of the remaining 22. The primary tumor site, unknown in 14/22 patients, was located during surgery only in 8 (57.1%). RESULTS: Due to tumoral spread, surgery was limited to exploration in 3 cases. Liver resections were performed in 19/22 patients (3 for palliation): 11/19 (57.9%) were major hepatectomies and in 8/19 (42.1%) cases they were accomplished by procedures for removing the primary tumor. Overall, curative procedures were carried out in 16/28 (57.1%). Resections were performed in 6 cases without the knowledge of the primary site. There was no operative mortality. Overall recurrence rate was 50.0%. Four-year actuarial survival was 92.6% after resection and 18.5% for patients that did not receive surgery (P < 0.001). CONCLUSIONS: Our experience confirms that the small number of patients makes the management of liver metastases from neuroendocrine tumors difficult to plan. In consideration of the satisfactory results achieved with an aggressive policy of resection, we advise referral of these patients to specialized liver units where major hepatic procedures, even if extended, can be safely performed.

Adult↗

Bronchogenic carcinoma in breast carcinoma patients.

Forty-eight female patients who developed bronchogenic carcinoma synchronously with or after the occurrence of breast carcinoma are reported. The object of the study was to review the radiographic findings for possible clues to the diagnosis of bronchogenic carcinoma and to ascertain the histologic diagnoses observed. In 40 patients on whom films were available, the original radiographs before surgery for bronchogenic carcinoma were examined. The clinical records of the 48 patients were also reviewed. Histologic diagnosis of primary bronchogenic carcinoma was required. A solitary pulmonary lesion in a patient with breast carcinoma, a cavitated lesion, or a lesion that failed to respond to appropriate therapy for metastatic breast carcinoma suggested the diagnosis of bronchogenic carcinoma. An increase in the frequency of small cell carcinoma and a decrease in the frequency of adenocarcinoma was seen in bronchogenic carcinomas developing 5 years or more after radiation therapy for breast carcinoma. It was concluded that the benefits of radiation therapy in selected patients far outweighed the risk of bronchogenic carcinoma.

Adenocarcinoma↗

Bilateral Wilms' tumor.

During a 16-year period, 49 children were treated for Wilms' tumor (WT); 7 were bilateral, 5 synchronous and 2 metachronous. The age at primary diagnosis was 6 months to 5 years (mean 2.4 years). All but 1 child received preoperative chemotherapy with tumor reduction. Unilateral nephrectomy was performed in 2 metachronous cases. In 3 synchronous WTs, the tumor was enucleated in 5 kidneys and a heminephrectomy was performed in 1 kidney with a double pelvis. Two children were not operated upon. At relapse in the contralateral kidney the tumor was enucleated. Three patients died of WT, 1 is alive with disease, and 3 are without evidence of disease. Renal salvage procedures were technically feasible without complications and are advocated to preserve renal function.

Antineoplastic Agents↗

Mortality experiences among 15+ year survivors of childhood and adolescent cancers.

BACKGROUND: Studies of childhood and adolescent cancer survivorship have tended to focus on limited survival intervals (e.g., 5 and 10 years). Our report evaluates gender-specific overall mortality, as well as mortality by age group, and by cause, among 15+ year survivors of cancer diagnosed during childhood or adolescence. PROCEDURE: This was a retrospective cohort study of 565 15+ year childhood cancer survivors from Roswell Park Cancer Institute's Long-Term Follow-Up Project. Sex- and age-specific person-years at risk were accumulated and applied to age-specific mortality rates for New York State, excluding New York City. Standardized mortality ratios (SMRs), and 95% confidence intervals, were calculated and compared to mortality risks of the general population. RESULTS: Second malignancy was the leading cause of death among male and female survivors (15/38 deaths, 39%). Excess overall mortality was noted among both males (SMR = 284) and females (SMR = 371). Significant mortality excesses were seen in both genders for deaths due to primary malignant neoplasms and secondary malignancies, as well as cardiac deaths among males. Excess mortality was noted across most age strata. In the scenario of no cancer relapse, overall mortality in both genders did not differ significantly from the general population. CONCLUSIONS: Long-term survivors of childhood and adolescent cancers continue to demonstrate significant excess mortality. However, overall mortality among 15+ year survivors without a relapse appears to be comparable to the general population. The leading cause of death among 15+ year survivors is second malignancy in this study, which represents a novel and important finding in terms of long-term follow-up.

Adolescent↗

Second malignant neoplasms in retinoblastoma. Fact and fiction.

Second malignant neoplasms (SMN) are distinct from primary neoplasms in site, time and histology. SMN may arise by chance or due to the influences of chemotherapeutic agents, therapeutic irradiation or genetic predisposition. Patients with the hereditary form of retinoblastoma (RB) appear genetically predisposed to the development of connective tissue tumours, particularly osteosarcoma. Therapeutic irradiation is an additional risk. Quantitation of the risk of SMN in RB patients may be influenced by selection biases and inappropriate analyses. Much of the biases in reported series arises from the limitations of single-centre studies. Loss of patients to follow-up, failure to adhere to properly defined criteria of SMN and to consider the risk of malignancy in the general population may have led to over-estimation of the risk of SMN in retinoblastoma patients.

Disease Susceptibility↗

Late effects of treatment of cancer in infancy.

Eighty-six children were diagnosed with cancer in infancy, followed for at lest 5 years, and assessed for late effects of disease and therapy. One child subsequently died from respiratory failure and 3 died from second primary cancers. Another patient survived second primary cancers of the skin. The high frequency of new cancers (4 observed, 0.09 expected) was attributable to host susceptibility factors and treatment effects. Kyphoscoliosis was diagnosed in 44 patients, 40 of whom had received radiotherapy to the spine. Other patients had neurologic deficits, pulmonary fibrosis, hypoplastic breasts, bowel adhesions, thyroid nodules, musculoskeletal defects, and liver fibrosis associated with tumor therapy. Sequelae of cancer were more common after treatment in infancy than in later childhood. Improved treatments and knowledge of natural history can reduce adverse effects of therapy.

Age Factors↗

A second brain tumour and irradiation.

Three patients are described in whom irradiation of 2750 rad or more was used in the management of primary brain tumours, and 21 years or more later a second brain tumour of a different type occurred. One of the new tumours was a meningioma and the other two were cerebral astrocytomas. There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma. Higher doses of radiation used for tumours in childhood are followed also by a late hazard of meningioma. There is insufficient evidence to implicate ionising radiations in the aetiology of gliomas. The oncogenic hazards of radiotherapy to the brain do not outweigh its therapeutic value in brain tumour.

Adult↗

Genetic alterations and MSI status in primary, synchronous, and metachronous tumors in a family with hereditary nonpolyposis colorectal cancer (HNPCC).

In colorectal cancer, different levels of microsatellite instability (MSI) have been described: high-frequency MSI, low-frequency MSI, and stable microsatellites. MSI-H characterizes a unique clinical and pathologic phenotype known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC). In this case, an increased incidence of synchronous and metachronous tumors has been reported, but there are few reports with standardized criteria of MSI in HNPCC-associated tumors. The authors attempted to establish whether tumors of the HNPCC spectrum with different levels of MSI could predict the development of metachronous carcinomas. We have examined the levels of MSI at loci frequently affected in colorectal cancers in primary, synchronous, and metachronous tumors in a family that fulfils the Amsterdam criteria for HNPCC. This family presents colorectal cancers, HNPCC-extracolonic tumors (endometrial and ureter), and tumors (breast and bladder) not described in the HNPCC spectrum. The tumors exhibited MSI-H, irrespective of their location and regardless whether they were primary, synchronous, or metachronous, with the only exception of both endometrial tumors that showed low-frequency MSI tumors (MSI-L). Our results suggest that not only colorectal tumors with MSI-H result in a potential marker for the determination of high-risk individuals for metachronous and synchronous tumors, but also MSI-L endometrial tumors might be considered as indicative of high-risk individuals.

Adult↗

Resection of liver metastases from colorectal cancer. Indications and results.

PURPOSE: This study was undertaken to determine the indications for and value of liver resection for metastases from colorectal cancer. METHODS: From 1978 through 1991, 66 patients were operated on for liver metastases from colorectal cancer. All patients had had a curative resection of their colorectal cancer. Forty resections of the liver were major anatomic resections. RESULTS: Five patients died in the postoperative period. All resections were intended to be curative, but in 16 of the patients the resection became noncurative. None of these patients lived more than two years after liver resection. Fifty patients with a curative resection had a three-year survival rate of 36 percent, postoperative death included. Recurrence in the liver was observed in 30 patients (60 percent) from 3 to 33 (median, 11) months after the liver resection. Four patients had repeated resections performed. Two of them are alive without recurrences 34 and 60 months after the first liver resection, respectively. The difference in survival between curative and noncurative liver resection was highly significant (P = 0.01). CONCLUSIONS: Sex, age, Dukes stage of primary colorectal cancer, synchronous or metachronous appearance of metastases, or number of metastases could not predict long-term prognosis. The only factors of predictive value were tumor size less than 4 cm in diameter, a free resection margin, and no extrahepatic tumor. If it is possible to do a curative resection, there should be few contraindications against liver surgery as it is the only treatment that can demonstrate long-term survival for approximately one-third of the patients, and it is the only possibility of a cure.

Actuarial Analysis↗

[The future of children cured of cancer: later morbidity].

The 476 children treated for solid malignant tumor from 1947 to 1968 at the Institut Gustave-Roussy, and living NED at 5 years, were reviewed after 5 to 36 years of follow-up (median 17 years). Two children were affected in the sibship in 9 families. Thirty patients died after 7 to 32 years, 15 from late evolution of their primary tumor, 7 from second cancer, and 8 from other causes. Late sequellae (3 lethal), mainly neurologic, orthopedic, endocrine, and others were observed in 271 patients, and not known in 48. A second tumor (19 malignant, 46 benign) occurred from 7 to 26 years after treatment, more than half in the previously irradiated area. These patients have presently 164 known children; two died in infancy, two have malformations. None has had tumor up until now. The long-term cure of cancer remains true in 95% of cases in our span of follow-up, with sequellae compatible with a useful life in most cases.

Adolescent↗