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Molecular analysis of synchronous and metachronous tumors of the lung: impact on management and prognosis.

Patients with pulmonary neoplasms have an increased risk for developing a second tumor of the lung, either at the same time or different times. It is important to determine if the second tumor represents an independent primary tumor (ie, a synchronous or a metachronous tumor, depending on whether it is present at the same time or a later time) or recurrence/metastasis, because it will significantly change the management and prognosis. Because the two tumors from the same patient are often morphologically similar, histologic examination alone may not be sufficient to distinguish between the two possibilities. We have attempted to approach this problem by microdissecting malignant cells and comparing patterns of loss of heterozygosity of multiple genes and chromosomal loci between paired tumors. We found that primary tumors of the lung and their metastasis share nearly identical patterns of loss of heterozygosity. In contrast, most synchronous and metachronous tumors as defined by the current arbitrary criteria appeared to be genetically different; therefore, they likely represented independent primary tumors. Rare synchronous tumors had similar genetic profiles, raising the possibility of recurrence/metastasis. Our data suggest that molecular analysis can help fingerprint tumors and has the potential to significantly impact management and prognosis of patients.

Adenocarcinoma↗

Primary gastric malignant lymphoma followed by gastric adenocarcinoma: report of 4 cases and review of the literature.

Four cases of primary gastric malignant lymphoma followed years later by adenocarcinoma of the stomach are described. Review of the literature revealed eleven other cases of these two lesions occurring in the same patient. In our four cases gastric adenocarcinoma developed many years after successful treatment of primary gastric lymphoma by partial gastrectomy. In three patients gastrectomy had been followed by radiation treatment to the upper abdomen. The relationship between the two tumors is discussed, including the possible role of treatment of the lymphoma in the development later of gastric adenocarcinoma. It is important to consider the possibility of the later development of a second primary gastric cancer in a patient who develops gastric symptoms, after successful treatment for primary gastric neoplasm.

Adenocarcinoma↗

Factors associated with the risk of second primary breast cancer: an analysis of data from the Connecticut Tumor Registry.

To examine further the epidemiology of contralateral primary breast cancer, a case-control analysis, utilizing information available from the Connecticut Tumor Registry, was conducted. Recent cases of second primary breast cancer were compared to control women who had survived a first breast cancer but had not developed a second. Three hundred and thirty eight incident cases of contralateral breast cancer diagnosed between 1979 and 1982 were identified and compared with an equal number of randomly selected controls and 336 controls frequency matched to the cases on the basis of age at initial cancer diagnosis and the calendar time elapsing since that diagnosis. Risk of second primary breast cancer was found to be significantly elevated among women whose initial cancer was lobular carcinoma and during the first year following diagnosis of the initial primary. Additionally, for women initially treated with radiotherapy, risk of a contralateral primary increased for 10-14 years following treatment, after which it declined. Among young women, having never married was protective whereas the opposite was found among older women. These findings and the methods used are discussed in the context of the epidemiology of both contralateral and initial breast primaries.

Adult↗

Multiple primary malignancies in association with soft tissue sarcomas.

BACKGROUND: Modern cancer treatment has increased the survival of patients with various malignancies substantially. One of the late sequelae of successful treatment is the development of a second malignant tumor. However, in many cases of second primary tumors, exposure to chemotherapy or radiation therapy is not evident, and it should be postulated that the putative mechanism for the development of the second tumor is different. In the current series, the association between soft tissue sarcoma (STS) in adults and the development of other primary malignancies was studied. METHODS: A retrospective search of the data files of 610 patients with STS or bone sarcomas who were treated at the study institution between January 1995 and December 1999 was performed. All files regarding patients with STS who developed a second malignant tumor were retrieved for analysis. RESULTS: Of 375 patients with STS, 28 (7.5%) developed other malignant neoplasms either before or after the diagnosis of STS. STS as the first tumor occurred in 14 patients (ages 16-72 years). Only three patients were treated with chemotherapy for their sarcoma. Radiation therapy was administered to five patients as an adjuvant to surgery for the first tumor. The second tumor types mainly included STS and renal cell carcinoma. The time interval between the diagnosis of the STS and the second malignancy was 0 (for synchronous tumors) to 21 years. Three patients developed a third primary tumor within 3 years after the diagnosis of the second tumor. The median overall survival was > 78 months. Fourteen patients (ages 35-87 years) had a first primary tumor other than STS (mainly breast carcinoma and genitourinary malignancies). The second tumors (mainly STS) appeared within 0 (for synchronous tumors) to 27 years. The median overall survival for the 14 patients in this group from the time of diagnosis of the first tumor was > 102 months. CONCLUSIONS: The phenomenon of two or three primary neoplasms developing in patients in whom one of the tumors was STS occurs at a rate of 7.5%, a significantly higher rate than that reported for the occurrence of STS among the general cancer population (1%). The majority of cases occur incidentally. The clinical implication includes the need to search for an occult second primary tumor in patients with STS as an integral part of their follow-up. This is especially true in patients with primary malignant fibrous histiocytoma who demonstrate a risk for developing a renal cell carcinoma.

Adolescent↗

[What can thoracic surgery accomplish in recurrent/second carcinoma of non-small-cell bronchial carcinoma?].

From 1990 to 2000, 2268 (29.9%) of 9600 lung cancer patients underwent resection for stage I to IIIA non-small cell lung cancer. Reinterventions were done in one hundred (3.5%) patients, for locoregional recurrence in 27, metachronous cancer in 42, metastasis or a third tumor in 31. A third intervention was performed in 23 patients and a fourth in two. The in-hospital mortality rate was 9%. The overall survival was 31.9% at five and 17.9% at ten years. The 5-year survival after the first intervention (reintervention) was 26% (11%) for local recurrence, 80.3% (27%) for metachronous cancer, 7% (0%) for recurrence of synchronous cancers and 0% (0%) for lung metastasis after a solitary primary lung cancer.

Carcinoma, Non-Small-Cell Lung↗

[Double cancers: a clinical analysis of 156 cases].

In order to study the causes of multiple primary carcinomas (MPC), and to give proper treatment, 156 patients with double cancers were analyzed retrospectively. The patients were admitted to the hospital from 1982 to 1987, accounting 0.47% of all hospitalized patients with malignant tumors in the same period. Out of them 86 patients were male, 70 patients were female. The age ranged from 17 to 80 old-year, the median 50 old-year. In 34 cases, the two cancers were synchronous in occurrence while in 122 cases were metachronous. The nasopharynx, lungs, large bowel and mammary gland were the most common sites of the MPC. The principle of treatment of the MPC was the same as that for ordinary primary carcinoma. The total 5-year survival rate was 34.6%.

Adolescent↗

[Angiosarcoma following teratocarcinoma: "mutation", successive malignancy or irradiation].

Angiosarcoma is a rare malignant soft-tissue tumor and affects preferably skin and adjacent subcutaneous tissue. Very rarely the tumor is radiation-induced. We report the case of a 28-year-old Swiss who developed an angiosarcoma of the gut 5 years after the successful therapy of metastasising teratocarcinoma of his right testis by surgery and radiation therapy. We discuss three possible etiologies for the genesis of the angiosarcoma, which appeared rapidly after the primary tumor at an unusual site in an unusual patient.

Adult↗

Second primary tumours in oropharyngeal squamous cell carcinoma.

Improved diagnostic techniques and more effective treatment concepts have resulted in a growing number of patients with oropharyngeal cancer diagnosed with second primary tumours. In order to evaluate the relative number of patients with second primary tumours and to estimate the efficacy of diagnostic procedures, a retrospective evaluation of 981 patients with oropharyngeal cancer, who were treated during 20 years in one single medical centre, was performed. In total, 9.2% of the patients were affected by secondary cancer, 1.5% from tertiary cancer and 0.2% from quartary cancer. Of the multiple cancers, 27.8% occurred synchronously and 72.2% metachronously. If the index tumour was located at the oral floor or the pharynx, the risk of second primary tumours was enhanced; if the index tumour was located at the lips or the tongue, the risk was reduced. The 5-year survival of all examined patients was 34.1%; the survival of patients with multiple cancers was 62.3% at the diagnosis of the index tumour and dropped to 30.5% at the diagnosis of an additional malignancy. Of the second primary tumours, 23.2% were diagnosed by panendoscopy. We conclude that among patients with oropharyngeal cancer, the presence of second primary tumours always has to be considered and that panendoscopy is a valuable tool for their diagnosis.

Adult↗

Changes in the course of cancer.

Many neoplasms cannot be cured but the life span of the patient afflicted with such diseases has in a remarkable number of cases been prolonged. The course of neoplastic diseases has been changed, improving life-style and survival on the one hand, but resulting in new side effects including multiple primary neoplasms on the other. In contrast to neoplastic diseases with aggressive acute development, we can observe an increasing number of neoplastic diseases with a chronic, prolonged that progress. To understand this it is necessary to remember that neoplastic diseases are heterogenic in nature, and also diseases of autonomic growth comprising modification of the host along with progression of the tumor.

Female↗

The risk of other primary cancer in patients with uveal melanoma: a retrospective cohort study of a Canadian population.

BACKGROUND: The incidence of second primary malignant tumours has doubled during the last 2 decades. These tumours now represent the sixth most common group of cancers. Many authors have described the presence of multiple primary cancers in patients with uveal melanoma. However, no studies have been performed using Canadian data. The purpose of this study was to describe the occurrence of other primary cancers diagnosed before or after uveal melanoma and to calculate the incidence of subsequent primary cancer in a Canadian cohort with uveal melanoma. METHODS: We conducted a retrospective study of a cohort of patients with uveal melanoma diagnosed between 1990 and 2002 at a university-affiliated centre in Montreal. We reviewed medical records to identify patients in whom other, unrelated primary malignant disease had been diagnosed. We used the standardized incidence ratio to calculate the risk of development of a second, unrelated cancer following the diagnosis of uveal melanoma. RESULTS: A total of 129 cases of uveal melanoma were diagnosed. Eighteen patients (14%) also had a diagnosis of an unrelated primary cancer. In nine patients the other cancer had been diagnosed first, and in nine patients the other tumour had been diagnosed after the uveal melanoma. There was no increased risk of development of any particular form of cancer studied for females or males. INTERPRETATION: In our Canadian cohort, statistical analysis showed no increased risk of a second cancer, overall or by organ site, in male or female patients with uveal melanoma. As uveal melanoma is a rare type of cancer, analyses of a much larger cohort may be needed to accurately estimate the risk of development of a second primary cancer in patients with uveal melanoma.

Adult↗

[Impact of diagnosis and treatment of early stage secondary tumors on outcome for the oncologic ORL patient].

OBJECTIVE: To study the incidence, location and stage of second primary tumours in patients with head and neck cancer and analyse the survival and outcome of patients with early-stage second primary tumours. METHODS: Retrospective chart review of patients treated for head and neck cancer from 1989 to 1993. Survival analyses and statistical comparisons with the Kaplan-Meier method and log-rank test. RESULTS: 99 of the 311 patients had second primary tumours. 45 patients had synchronous second primary tumours and 54 metachronous second primary tumours, diagnosed at an early stage (stage 0 or I) in 78 and 63% of cases respectively. Patients with second primary tumours had a significantly (p = 0.03) lower survival rate than patients with single tumour. However, for patients with early stage second primary tumours survival was not significantly decreased (p = 0.3). DISCUSSION: This study confirms the high incidence of second primary tumours and their negative impact on the outcome of patients with head and neck cancer. Early diagnosis and treatment of second primary tumours results in a survival rate very similar to that of patients with a single head and neck cancer. This provides indirect evidence that in patients with curable initial head and neck cancer intensive screening for second primary tumours may result in an improved overall outcome.

Adult↗

[Sarcoma of soft tissues induced by radiation. Presentation of a case and review of the literature].

The clinical history of a 57 y/o female who had breast cancer diagnosed at 40 years of age and who was treated with right radical mastectomy followed by irradiation of the right chest and adjacent lymphatics is presented. Recurrences of the breast cancer were treated with combination chemotherapy. Eighteen years after the original diagnosis and irradiation she presented with a new primary tumor of a different histologic type in the site of the prior irradiation. This tumors had an extremely aggressive, fatal course.

Female↗

Multiple primary tumors in patients diagnosed with hypopharyngeal cancer.

OBJECTIVE: There have been few series to report on the incidence of multiple primary tumors associated with hypopharyngeal cancer. A unique consecutive patient group in a closed community who were treated by a single surgeon was available. The incidence and effect of multiple primary tumors were unknown. STUDY DESIGN: We sought to assess (1) the incidence of multiple primary tumors among patients with hypopharyngeal cancer who were treated at a tertiary center, (2) the incidence of synchronous and metachronous tumors, and (3) the location of these multiple primary tumors and their effect on patient survival. METHODS: We conducted a retrospective study of case notes of 150 consecutive patients with hypopharyngeal malignancy treated by a single surgeon between 1983 and 1998. Information was compiled from the patients' medical records and death data from the Family Health Services Authority. RESULTS: Thirty-four patients had multiple primary tumors (22.6%). There were 22 men and 12 women; piriform fossa tumor was seen in 21 men and 6 women, and postcricoid space tumor was seen in 6 women and 1 man. Second primary tumors were synchronous in 7 patients, subsequent to hypopharyngeal tumor in 5 patients, and antecedent to hypopharyngeal tumor in 14 patients. Eight patients had 2 primary tumors, of which 4 were synchronous, 4 were subsequent, and 8 were antecedent to hypopharyngeal malignancy. On the last review (2001), 3 patients were alive, and 31 had died: 17 had died from primary malignancy, 11 from another malignancy, and 3 from unrelated causes. CONCLUSION: The presence of second primary tumors in hypopharyngeal cancer is higher than previously reported, and their presence had a significant effect on the patients' survival.

Aged↗

Multiple primary malignancies in renal cell carcinoma.

PURPOSE: We determine the incidence and nature of multiple primary malignancies in patients with renal cell carcinoma, and whether these patients have an increased risk of a second primary malignancy. MATERIALS AND METHODS: Between July 1989 and January 1997, 551 patients underwent an operation for renal cell carcinoma. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. The observed number of subsequent malignancies after diagnosis of renal cell carcinoma was compared to the expected number based on age, race and sex specific 1990 to 1994 incidence rates from the United States Surveillance, Epidemiology and End Results data using the Poisson test. RESULTS: The number of primary malignancies, including cutaneous malignancies, was at least 1 in 148 patients (26.9%), at least 2 in 34 (6.2%), at least 3 in 6 (1.1%) and 4 in 1 (0.2%). Other malignancies were antecedent in 85 cases (45.0%), synchronous in 74 (39.4%) and subsequent in 30 (16.0%). The most common other primary malignancies were breast, prostate, colorectal and bladder cancer, and non-Hodgkin's lymphoma. Only men with renal cell carcinoma had an increased risk of bladder cancer (standardized incidence ratio 4.3, p = 0.0067). CONCLUSIONS: Breast, prostate, colorectal and bladder cancer as well as non-Hodgkin's lymphoma were the most common other primary malignancies. Men with renal cell carcinoma have an increased risk of subsequent bladder cancer.

Adult↗

Postirradiation sarcoma in retinoblastoma. Induction or predisposition?

An alarmingly high rate of postirradiation sarcomas following treatment for retinoblastoma has been described in the literature. We present four new cases and report 57 others from the English literature. Osteogenic sarcoma was the predominant histologic type (58%), followed by fibrosarcoma (21%) and various other sarcomas (21%). The average latency period between irradiation and development of the second primary (sarcoma) was 12.4 years. Irrespective of irradiation, a genetic linkage between retinoblastoma and osteogenic sarcoma on the 13q14 chromosome is recognized. Through a pleiotropic effect of this same chromosome, a predisposition for other sarcomas may exist as well. Finally, a strong role for radiation induction is proposed for all of these postirradiation sarcomas. This is based on the increased number of sarcomas arising in the field of prior irradiation (sites uncharacteristic of spontaneously occurring primary sarcomas) and the prolonged latency periods.

Adult↗

Prognostic significance of synchronous and metachronous bilateral breast cancer.

Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast, but the clinical significance of this development is unclear. The purpose of this study was to assess the impact of synchronous bilateral breast cancer or the development of a metachronous contralateral breast primary on the prognosis. In a series of 3210 women age < or = 70 years treated between 1975 and 1995 for primary operable breast cancer, 106 were identified to have bilateral breast cancer. Of these women, 26 were noted to have synchronous bilateral breast primaries (0.8%), and 80 developed a contralateral breast cancer after treatment for an initial primary breast cancer. Using life-tables analysis, there was a significant difference in survival between women with unilateral breast cancer, those with synchronous bilateral breast cancers, and those with metachronous contralateral breast with survivals at 16 years of 53.8%, 42.4%, and 60.1%, respectively (p < 0.0001), from the date of the diagnosis of the first primary tumor. There was no difference in survival seen between the three groups when survival was calculated from the date of diagnosis of the second primary in cases of metachronous contralateral breast cancer (p = 0.31). When contralateral breast cancer was incorporated as a time-dependent covariate in a Cox multivariate model together with the three factors used to determine the Nottingham Prognostic Index (invasive tumor size, grade, and lymph node stage), contralateral breast cancer continued to be a significant prognostic determinant (p = 0.02). The survival of women with synchronous bilateral breast cancer or metachronous breast cancers diagnosed within 2 years of the original primary was worse than those with unilateral disease. However, the time duration to metachronous contralateral breast cancer did not have prognostic significance in a multivariate model compared with the prognostic features of the original primary.

Adult↗