Second Tumors In Patients Research Articles

Multiple primary malignant neoplasm in patients with laryngeal carcinoma.

The aim of this study was to study the incidence, localization, and nature of second primary tumors arising in patients with primary laryngeal carcinoma and their correlation with the site, staging, and grade of differentiation. Between 1979 and 1996, 877 patients underwent laryngeal surgery (850 male and 27 female; age range = 30.5-76 years). The second primary tumor was multicentric in 7 cases (14%), systemic in 16 cases (33. 3%), and "coincidental" in 25 cases (52%). In 3 cases the tumors were simultaneous, in 7 cases they were synchronous, and in 38 cases they were metachronous. In the 48 patients with multiple primary malignant neoplasm, the index tumor was glottic in 38 cases and supraglottic in the remaining 10, but the incidence of second tumors in these two groups was virtually matching, respectively: 38/709 (5. 3%) and 10/168 (5.9%). This study did not identify any correlation between the second primary tumor and the extension of the first neoplasm (T) and the presence of laterocervical lymph node metastases (N). Our data showed a higher incidence of second tumor in patients having G1 carcinomas compared with the other series with G2 and G3 carcinomas. As far as survival rates are concerned, a significant reduction was observed in patients developing a second primary tumor, regardless of whether the index tumor was glottic or supraglottic. The incidence of new tumors in patients with laryngeal carcinoma is not linked to the site, size, staging, or grade of differentiation of the index tumor.

Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias.

The nucleoside analogs fludarabine, 2'-deoxycoformycin (DCF), and 2-chlorodeoxyadenosine (CdA), commonly used in the treatment of patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL), are associated with myelosuppression and profound and prolonged immunosuppression. These complications raise the possibility of an increase in secondary malignancies in patients whose disease already places them at greater risk. The purpose of the present study was to assess the frequency of second tumors in patients with CLL who are treated with fludarabine and in patients with HCL who are treated with DCF and CdA. We reviewed the long-term follow-up data for 2,014 patients treated on National Cancer Institute Group C protocols with fludarabine for relapsed and refractory CLL and with DCF and CdA for HCL using a Second Cancer Report. The numbers of observed and expected secondary tumors were compared. Median follow-up periods for the DCF (n = 409), fludarabine (n = 724), and CdA (n = 979) studies were 6.9, 7.4, and 5.1 years, respectively. The 111 malignancies were most commonly lymphoma (25 patients), prostate (19), lung (15), colorectal (nine), bladder (six), and breast (six), but also CNS, stomach, ovary, head and neck, melanoma, sarcoma, testicular, and myeloid leukemias. Compared with age-adjusted 1994 Surveillance and Epidemiology End-Results rates for the general population, the observed/expected frequencies for DCF, fludarabine, and CdA were 1.43 (95% confidence interval [CI], 0.93 to 2.10), 1.65 (95% CI, 1.04 to 2.47), and 1.50 (95% CI, 1.14 to 1.93), respectively, indicating a significant (at P =.05) increase in risk for patients treated on the latter two protocols compared with a normal population. However, these values are consistent with the increase already associated with these diseases. Despite their immunosuppression, nucleoside analogs can be safely administered to patients with CLL or HCL without a significantly increased risk of secondary malignancies.

Incidence of second neoplasms in patients with MALT lymphoma: No increase in risk above the background population

Lymphomas of mucosa associated lymphoid tissue (MALT) are a special type of extranodal lymphoma, possibly related to chronic antigenic stimulation. Increased cancer susceptibility may also contribute to the development of MALT lymphoma (MALToma). It has been suggested that patients with MALToma have an increased incidence of other malignancies. We retrospectively reviewed the histology and clinical records of 147 patients with MALToma, including 51 cases of gastric MALToma. The incidence of any second malignancy was confirmed with a provincial registry. The relative rates of cancer, excluding MALToma, were calculated relative to the background population of the same age group and secular year. A total of 41 tumors occurred in 32 patients (21%), including 22 solid tumors. The incidence of solid tumors in the gastric MALToma group was 15%. Seven patients had two or more second malignancies. Cancer occurred before diagnosis of MALToma in 29 cases, concurrent with MALToma in three, and after MALToma in nine. Follow-up of the surviving patients is short (median 17.6 months). The relative rate from birth of a second malignancy was 0.86 in the whole group (90% confidence interval (CI): 0.62-1.16) and 0.95 (90% CI: 0.55-1.54) in the gastric MALToma group. The rates were roughly the same if skin cancers were excluded. The incidence of second cancers in this series is similar to previous reports. However, when compared to an age-matched population followed for the same period of time, MALToma patients do not appear to have a statistically significant increased rate of cancers.

Clinical characteristics of metachronous bilateral testicular tumors in the chemotherapeutic era.

We wanted to present the results of our experience with bilateral testis tumor and to suggest the effects of chemotherapy in suppressing the development of second primary testicular tumors. Between 1978 and 1997, 2,345 patients were treated for testicular tumor at The University of Texas M. D. Anderson Cancer Center. Of these, 2,107 had germ cell cancers. There were 22 (0.94%) cases of bilateral testicular tumor in the overall patient population and 21 (1.0%) cases among patients with germ cell cancer. We reviewed the medical records to determine the incidence of the histological subtype, the incidence of metachronous versus synchronous formation of contralateral tumors, and tumor stage in this patient population. We also examined the effect of chemotherapy in treating the first tumor and preventing the occurrence of a second tumor. Finally, we compared the effect of ultrasonography, serum tumor marker elevation, and physical examination in detecting second tumors. Only one contralateral germ cell tumor developed synchronously; all others developed metachronously. Fifty percent of first tumors were seminomas, compared to 55% of second tumors. The histologic concordance rate for first and second tumors was 35%. Tumor stage was higher among first tumors than second tumors. The majority of second tumors in patients who received chemotherapy for first malignancies tended to be metachronous seminomas. Ultrasonography detected 6 of 21 (28.6%) contralateral tumors before they were evident by physical examination or serum tumor marker elevation. Seminomas were more prevalent among patients with bilateral germ cell disease than patients with unilateral disease. Chemotherapy, when used as treatment for first tumors, may have some effect in preventing the development of nonseminomatous germ cell tumors in the contralateral testicle. Close follow-up of the contralateral testis with ultrasonography is essential for early detection of second tumors. The outcome for patients with bilateral testicular germ cell cancer is excellent, secondary to early detection.

Second cancers after medulloblastoma: population-based results from the United States and Sweden.

Medulloblastoma, one of the most common central nervous system (CNS) tumors in children, requires aggressive multimodality therapy including surgery, radiation therapy, and occasionally chemotherapy. Given its intensive treatment regimen and improved survival during the past 20 years, it is likely that a cohort of survivors will result who may incur consequences of therapy, including a second cancer. We used population-based data from the United States and Sweden to estimate risks of second neoplasms in patients with histologically confirmed medulloblastoma (n = 1,262). Overall, there was a 5.4-fold excess of second neoplasms (95 percent confidence interval = 3.3-8.4) based on 20 observed and 3.7 expected cancers. The second cancers occurred eight to 432 months after initial diagnosis (median, 73 months) with significantly elevated ratios for all intervals examined except for less than one year after initial diagnosis. Significantly elevated risks were seen for cancers of the salivary glands, cervix uteri, brain and CNS, thyroid gland, and acute lymphoblastic leukemia. Of the 15 second cancers with treatment data, seven occurred in the radiation field or within areas of scatter while two others may have been radiation-related. Although based on small numbers of second cancers, the results suggest that as survival increases, some patients with medulloblastoma will have an increased risk of a second cancer, particularly a radiation-related cancer. Thus, as survival improves, late-occurring consequences of diagnosis and treatment will need to be carefully assessed. Identification of patients hypersensitive to radiation therapy, such as those with Gorlin Syndrome, should also be attempted in order to reduce the sequelae from intensive radiation exposure.

Breast carcinoma is the most common second neoplasm in patients who survive Hodgkinʼs disease

Breast carcinoma is the most common second neoplasm in patients who survive Hodgkinʼs disease

Role of folylpolygutamate synthetase (FPGS) in antifolate chemotherapy; a biochemical and clinical update.

Even though folate antimetabolites were introduced over forty years ago, they continue to be the backbone of many active chemotherapeutic regimens used by medical and pediatric oncologists. The recognition of polyglutamylation by folylpolyglutamate synthetase (FPGS) as an important metabolic step in the "activation" of classical antifolates and novel drugs aimed at thymidylate synthase (TS) and de novo purine synthesis, has resulted in renewed interest in this class of drugs. In addition, the emergence of secondary neoplasms in patients treated with alkylating agents and topoisomerase inhibitors in contrast to the exceptional safety record of antimetabolites, underscores the need for clinical trials that incorporate new strategies with known active antimetabolites and novel promising agents. In that context, FPGS is an important target for further laboratory and clinical investigations.

Hairy cell leukemia: Treatment results and association with secondary malignancy

American Journal of HematologyVolume 48, Issue 4 p. 291-291 Letters and CorrespondenceFree Access Hairy cell leukemia: Treatment results and association with secondary malignancy Y. L. Kwong, Y. L. Kwong University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorR. Liang, R. Liang University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorE. Chiu, E. Chiu University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorD. W. Chan, D. W. Chan University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorT. K. Chan, T. K. Chan University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this author Y. L. Kwong, Y. L. Kwong University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorR. Liang, R. Liang University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorE. Chiu, E. Chiu University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorD. W. Chan, D. W. Chan University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this authorT. K. Chan, T. K. Chan University Department of Medicine, Queen Mary Hospital, Hong KongSearch for more papers by this author First published: April 1995 https://doi.org/10.1002/ajh.2830480421Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Kwong YL, Wong KF, Chan LC, Liang RHS, Chan JKC, Wei D, Chiu EKW, Chu YC, Todd D, Chan TK: The spectrum of chronic lymphoproliferative disorders in Chinese people-an analysis of 64 cases. Cancer 74: 174– 181, 1994. 2 Liang R, Chan V, Chan TK, Wong T, Chiu E, Lie A, Todd D: Detection of immunoglobulin gene rearrangement in lymphoid malignancies of B-cell lineage by seminested polymerase chain reaction gene amplification. Am J Hematol 43: 24– 28, 1993. 3 Machii T, Tokumine Y, Inoue R, Kitani T: Predominance of a distinct subtype of hairy cell leukemia in Japan. Leukemia 7: 181– 186, 1993. 4 Filleul B, Delannoy A, Ferrant A, Zeenebergh A, Bosly A, Doven C: A single course of 2-chlorodeoxyadenosine (2-CdA) does not eradicate leukemic cells in hairy cell leukemia (HCL) Patients achieving complete remission. Blood 82(suppl): 142a, 1993. 5 Kampmeier P, Spielberger R, Dickstein J, Mick R, Golomb H, Vardiman JW: Increased incidence of secondary neoplasms in patients treated with interferon α 2b for hairy cell leukemia: A clinicopathologic assessment. Blood 83: 2931– 6, 1994. Citing Literature Volume48, Issue4April 1995Pages 291-291 ReferencesRelatedInformation

Increased Incidence of Second Neoplasms in Patients Treated With Interferon α 2b for Hairy Cell Leukemia: A Clinicopathologic Assessment

AbstractWe report that there is an unexpectedly high incidence of second neoplasms in patients after treatment of hairy cell leukemia (HCL) with interferon α 2b (IFN). In a cohort of 69 patients with HCL entered in a protocol using IFN as the primary treatment, and followed thereafter for a median of 91 months (range, 0.2 to 109 months), 13 patients (19%) developed a second neoplasm. Six neoplasms were of hematopoietic origin, whereas the remaining seven were adenocarcinomas. The expected number of second tumors in this cohort is three (based on calculations from the National Cancer Institute’s SEER data), so the excess frequency (observed:expected) is 4.33. However, the excess frequency is even greater for the hematopoietic neoplasms; the expected frequency is 0.15, whereas six hematopoietic tumors occurred, for an observed:expected ratio of 40. In general, the second neoplasms have behaved aggressively, and the median survival after diagnosis of the second neoplasm was only 8.8 months. Although we cannot entirely exclude the possibility that IFN therapy has some direct oncogenic effect, we suspect that increased frequency of second tumors is related to prolonged survival of patients who are immunocompromised because of HCL and thus prone to develop second tumors. If so, the frequency of second neoplasms in patients with HCL may be even greater in the future with continued improvements in therapy.

Incidence of non-Hodgkin's lymphoma in patients treated for Hodgkin's disease.

The purpose of this study was to evaluate the incidence of non-Hodgkin's lymphoma (NHL) as a second tumor in patients treated for Hodgkin's disease (HD), as well as to establish the role of different variables in its appearance. Between January 1973 and June 1988, 101 patients with HD were treated according to the stage, with chemotherapy and/or radiotherapy. Complete remission was obtained in 87 patients. Five patients developed secondary NHL between the 77th and 124th month of complete remission. The median follow up was 73 months (range 3-227 months). The incidence of second NHL in our series was, 0%, 4.6% (CI 0-11%) and 17% (CI 4-32%) at 5, 10 and 15 years respectively. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, splenectomy, histology, stage and treatment modality) showed that the only statistically significant variable was the treatment received (p < 0.01). Cumulative incidence of NHL at 15 years, ranged from 0% for patients treated with radiotherapy or chemotherapy alone to 39.6% for those who received combined therapy (p = 0.002). We can conclude that the use of chemotherapy plus radiotherapy for treatment of HD increases the risk for the development of second NHL.

Second neoplasms in patients with carcinomas of the vocal cord: Incidence and implications for survival

A retrospective analysis was performed for 218 patients who were managed for carcinomas of the glottic larynx from 1975 to 1988. With a median follow-up of 51 months (range: 24 to 120 months), 41 patients developed a second malignant neoplasm. Six patients had synchronous and 35 had metachronous second malignant neoplasms. The median interval between the diagnosis of glottic carcinoma and a second malignant neoplasm was 31 months. This median interval increased to 43 months when only the metachronous tumors were analyzed. The average annual risk of developing a second malignant neoplasm in a 10-year period was 3.14% Seventy-one percent of them occurred in the upper aerodigestive tract or lungs. When analyzed according to the initial stage of the glottic carcinoma, 23 of 145 (16%) patients with TI or T2 glottic carcinomas developed a second malignant neoplasm, whereas 18 of 73 (25%) patients with T3 or T4 lesions did so. For the T1 T2 group, the average annual risk was 2.5%, as compared to 4.8% for the T3 T4 group ( p = 0.023). The development of a second malignant neoplasm adversely affected survival. The 10-year actuarial survival for those patients who did not develop a second malignant neoplasm was 45%, as compared to 19% for those who did develop a second malignant neoplasm ( p = 0.008). Although second malignant neoplasms occurred in only 19% of the total patient population, their impact on the survival rate of the overall population was equal to that of glottic carcinomas. The median survival after the diagnosis of a SMN was 6 months. The high incidence of second malignant neoplasms in patients with glottic carcinomas warrants careful follow-up and clinical investigation of the use of chemopreventive agents.

The clinical behavior of radiation-induced thyroid cancer in patients with prior Hodgkin's disease

Second primary neoplasms are occurring with increasing frequency. Despite growing literature on the incidence and etiology of this phenomenon, very little has been documented about the clinical aspects and biological behavior of these tumors. As our experience has hinted at a worse prognosis for second primaries, we thought it of interest to study this phenomenon for one type of tumor. We reviewed 32 cases of thyroid cancer arising as a second neoplasm in patients with Hodgkin's disease and compared various clinical characteristics to reported series of de novo (non-radiation-induced) thyroid cancer. Thyroid cancer, as a second primary, occurred more frequently in males with a more malignant histology and was diagnosed at a more advanced stage. The survival appears to be worse. The behavior of radiation-induced thyroid cancer in a host with prior malignant neoplasia appears to be more aggressive than that of both de novo (non-radiation-induced) thyroid cancer and radiation-induced thyroid cancer in a host with no prior malignancy. The selected nature of the cases precludes any firm conclusions. This type of information should be collected prospectively for all secondary malignancies as it may have an impact on the clinical management of these patients.

A Case of Extensive Gastrointestinal Involvement of Malignant Lymphoma Associated with Early Gastric Carcinoma

Abstract: Described is a 59 year old Japanese man With malignant lymphoma involving the stomach, duodenum, terminal ileum, colon and rectum, who developed early gastric carcinoma. Repeated gastroduodenoscopy revealed various appearances of the gastrointestinal involvement in malignant lymphoma, such as giant folds, polypoid lesions, and ulcerations, in addition to a depressed lesion of early gastric carcinoma. Colonoscopy also showed multiple polypoid lesions throughout the large bowel. Though the gastrointestinal involvement in malignant lymphoma is not rare, diffuse multiple polypoid lesions in the entire large bowel as seen in our case have rarely been endoscopically described.The coexistance of malignant lymphoma and gastric carcinoma in our case might be only a coincidence, though some reports of an increasing incidence of second tumors in patients with malignant lymphoma have been published. Further consideration will be needed as to the relationship between malignant lymphoma and the occurence of a second malignancy.

Incidence of Second Neoplasms in Patients with Bilateral Retinoblastoma

The cumulative incidence of second neoplasms in 215 patients with bilateral retinoblastoma was calculated using the life-table method. Second tumors developed in 4.4% of the patients during the first 10 years of follow-up, in 18.3% after 20 years, and in 26.1 % after 30 years. The 30-year cumulative incidence was 35.1 % for the 137 patients who received radiation therapy compared with an incidence rate of 5.8% for the 78 patients who did not receive radiation. In the 137 patients who received radiation, second tumors developed both inside and outside the field of therapy. There was a 30-year incidence rate of second tumors of 29.3% within the field of irradiation and 8.1 % outside the field. The rate outside the field of irradiation (8.1 %) was similar to that observed in nonirradiated patients (5.8%). Our findings indicate that carriers of the retinoblastoma gene have an increased incidence of second tumors, and that the incidence rate is further increased in patients who receive radiation therapy.

Radioprotectors in treatment therapy to reduce risk in secondary tumor induction

Radiation and chemotherapy are two effective modalities in the arsenal of cancer therapy. Because of increased awareness by the general public and earlier detection and improved diagnosis, more and more patients are being effectively treated and cured of cancer. Unfortunately, most of these therapeutic agents are, for the most part, extremely mutagenic and/or carcinogenic. When multiple agents such as combined radiation and chemotherapy are used, the carcinogenic potential may rise sharply. For example, patients treated for Hodgkin's disease appear to exhibit a relatively high risk for therapy-induced acute myelogenous leukemia (Bartolucci et al . , 1983) and non-Hodgkin's lymphoma (Jacquillat et al . , 1984). Thus, the risk of therapy-induced secondary tumors in patients having potentially curable disease is becoming a significant health problem (Rowley et al . , 1981; Penn, 1982; Chak et al . , 1984; Jacobs and Gale, 1984; Dorr and Coltman, 1985). Considerable effort has been devoted to developing treatment protocols that maximize therapeutic gain. Emphasis has been directed toward improving the ability of patients to withstand the acute deleterious effects of these therapeutic agents. The intent has been to attempt to enhance a sparing or differential protective effect to dose-limiting normal tissues. It is this rationale that has prompted considerable study of a class of chemical agents collectively referred to as radioprotectors. Specifically, the compound S-2(3-aminopropylamino)ethylphosphorothioic acid (WR-2721, ethiofos) has been investigated because of its reported ability to differentially protect normal tissues compared with neoplastic tissues (Yuhas et al. , 1980; Phillips, 1980). Evaluation of this compound for use in radiation therapy is currently under way at a number of institutions. Recently, however, investigators have reported that WR-2721 can also significantly protect against the induction of tumors in rodents by ionizing radiation (Milas et al . , 1984). This observation is especially intriguing since it suggests that this class of agents might also be effective fi~r use in reducing the risk of late-effects damage such as the formation of therapy-induced secondary tumors.

Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality Therapy-The Yale Experience.

In the article by Koletsky et al "Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality Therapy-The Yale Experience" (Journal of Clinical Oncology 4:311-317, 1986), an error was made in the footnote on page 311 which described the composition of MVVPP. The corrected footnote appears below. *MVVPP = nitrogen mustard (0.4 mg/kg on day 1 of cycle); vinblastine (6 mg/m2 on days 22, 29, and 36); vincristine (1.4 mg/m2, 2 mg maximum dose, on days 1, 8, and 15); procarbazine (100 mg/d on days 22 through 42); prednisone (40 mg/m2 on days 1 through 15 for cycles 1, 3, and 5 only).

Somatic events unmask recessive cancer genes to initiate malignancy

A heritable mutation predisposes an individual to certain childhood malignancies, such as retinoblastoma and Wilms' tumor. The chromosomal locations of the genes responsible for the predisposition are known by linkage with chromosomal deletions and enzyme markers. A study of these tumors in comparison to the normal constitutional cells of the patients, using enzyme and DNA markers near the predisposing genes, has shown that these genes are recessive to normal wild-type alleles at the cellular level. Expression of the recessive phenotype (malignancy) involves the same genetic events that were observed in Chinese hamster cell hybrids carrying recessive drug resistance genes. In both the experimental and clinical situations, the wild-type allele is most commonly eliminated by chromosome loss with duplication of the mutant chromosome. Simple chromosome loss and mitotic recombination have been documented in both systems. In the remaining 30% of cases, inactivation or microdeletion of the wild-type allele are assumed to be responsible for expression of the recessive phenotype. Osteosarcoma is a common second tumor in patients who have had retinoblastoma. Studies with markers in osteosarcoma show that these tumors also result from unmasking of the recessive phenotype by loss of the normal allele at the retinoblastoma locus, whether or not the patient had retinoblastoma. Subsequent chromosomal rearrangements and amplification of oncogenes that occur in these homozygous tumors provide progressive growth advantage. In other malignancies, in which studies have so far focused on oncogene amplification and chromosomal rearrangements, unmasking of recessive mutations may also be the critical initiating events.

Secondary Neoplasms in Patients Treated for Cancer: Etiology and Perspective

The exact risk of secondary neoplasms in patients treated for cancer is difficult to ascertain due to a nonspecific increased risk, a possible genetic or congenital predisposition, and tumor multicentricity. Second tumors now considered ''treatment-related'' may, in fact, be ''syndrome-related,'' as in the case with secondary osteosarcoma in patients with retinoblastoma. A wide variety of second tumors have been described with solid tumors having latency periods of 10 years and with leukemia 5 years. Recently secondary lymphomas have been reported in Hodgkin's disease patients which may be related to their altered immunity. The 10-year risk of developing second cancers in patients with Hodgkin's disease of pediatric malignancies is approximately 10%, but the risk for all newly diagnosed cancer patients is below 1%. Aggressive treatment has improved curability; however, prolonged administration of chemotherapy, especially alkylating agents, and the use of radiotherapy plus chemotherapy have been major risk factors in the current excess of second cancers. Carcinogenic treatment should be avoided; however, patient curability must not be compromised until less toxic treatments are proven to be equally effective.

Non-Hodgkin's lymphoma and acute myeloblastic leukemia.A report of 12 cases and review of the literature

Twelve cases of non-Hodgkin's lymphoma and acute myeloblastic leukemia or one of its variants are reported. An additional 33 cases from the literature are reviewed. The mean interval between the diagnosis of lymphoma and acute leukemia is 5.2 years. In 5 patients the two diseases occurred simultaneously or within 6 months of each other. All but 10 of the 45 patients received radiation therapy for their lymphoma. Nine patients had either total nodal or total body irradiation or both. Eight patients received chemotherapy alone. No patient was untreated. Survival after the diagnosis of acute leukemia ranged from 3 days to 14 months, with a median of 3 months. Four patients achieved complete hematological remission following antileukemic therapy. Acute leukemia is estimated to occur in patients with non-Hodgkin's lymphoma in New York State with a 37-fold increased frequency over the expected number. Although acute leukemia may occur in a higher than expected frequency in patients with non-Hodgkin's lymphoma because of an increased risk of a second neoplasm in patients with a primary tumor, it seems more likely that the acute leukemia may be related to the radiotherapy and/or chemotherapy administered to treat the lymphoma. Late death from leukemia after chemotherapeutic or radiotherapeutic remission of advanced non-Hodgkin's lymphoma is preferable to morbidity and/or early death from untreated or inadequately treated lymphoma.

Second Tumors in Nonirradiated Bilateral Retinoblastoma

We reviewed the records of 1,323 patients with retinoblastoma treated here between 1922 and 1978. Twenty-eight patients underwent bilateral enucleation alone and received no additional treatment for their advanced tumors. Of the 28 patients, 22 (92%) survived. Four patients were lost to follow-up, and two died of metastatic retinoblastoma. Of 22 survivors of bilateral retinoblastoma treated with enucleation alone, three developed second tumors at a mean of 15.3 years after bilateral enucleation. One patient developed a rhabdomyosarcoma in the left temple region, the second patient developed an osteogenic sarcoma of the right femur, and the third developed a malignant melanoma of the left thigh. All three patients died of their disease. The incidence of second tumors in patients who survived bilateral retinoblastoma treated without radiation was 14% (three patients), which is comparable to a series previously reported in which patients were treated with enucleation and irradiation.