Occurrence Of Other Malignancies Research Articles

The heterogeneous cancer phenotype of individuals with biallelic germline pathogenic variants in CHEK2

PurposeFemales with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals with monoallelic CHEK2 gPVs. This study is aimed at expanding the knowledge on the occurrence of other malignancies. MethodsExome sequencing of individuals who developed multiple primary malignancies identified 3 individuals with the CHEK2 (NM_007194.4) c.1100del p.(Thr367MetfsTer15) loss-of-function gPV in a biallelic state. We collected the phenotypes of an additional cohort of individuals with CHEK2 biallelic gPVs (n = 291). ResultsIn total, 157 individuals (53.4%; 157/294 individuals) developed ≥1 (pre)malignancy. The most common (pre)malignancies next to breast cancer were colorectal- (n = 19), thyroid- (n = 19), and prostate (pre)malignancies (n = 12). Females with biallelic CHEK2 loss-of-function gPVs more frequently developed ≥2 (pre)malignancies and at an earlier age compared with females biallelic for the CHEK2 c.470T>C p.(Ile157Thr) missense variant. Furthermore, 26 males (31%; 26/84 males) with CHEK2 biallelic gPVs developed ≥1 (pre)malignancies of 15 origins. ConclusionOur study suggests that CHEK2 biallelic gPVs likely increase the susceptibility to develop multiple malignancies in various tissues, both in females and males. However, it is possible that a substantial proportion of individuals with CHEK2 biallelic gPVs is missed as diagnostic testing for CHEK2 often is limited to individuals who developed breast cancer.

Additional malignancies shorten overall survival in chronic lymphocytic leukemia irrespective of chromosomal aberrations: A retrospective cohort study.

The aim of this study was to determine the incidence of other malignancies (OMs) in patients with chronic lymphocytic leukemia (CLL) and to identify parameters associated with the occurrence of OMs in addition to CLL. This retrospective cohort study was conducted by examining the records of CLL patients who applied to a tertiary hospital between January 2013 and December 2021. The cases were divided into 2 groups, CLL (n = 107) and CLL + OM (n = 25), according to the presence of additional malignancy. Lymphocyte count (P = .014), white blood cell count (P = .006), and hemoglobin (P = .034) were significantly higher in the CLL group. Rai stage IV percentage (P = .015), Binet stage B percentage (P = .043), progression, and sepsis percentages (P = .008) were significantly higher in the CLL + OM group. Overall survival time was significantly lower in the CLL + OM group (P = .032). Most OMs had been diagnosed before CLL (63.64%) in the no-treatment group, while the majority of OMs were diagnosed after CLL (78.57%) in the treatment group (P = .032). CLL patients with OM had a more advanced CLL stage, and survival was significantly shorter in these patients. In addition, CLL-associated OM appears to occur more frequently in the post-treatment period.

Double hit

Gastrointestinal Stromal Tumours (GISTs) are rare but remain the most common mesenchymal tumour of the Gastrointestinal tract (GIT). The asynchronous occurrence of other malignancies in patients with GIST during the clinical course is relatively common. However, the synchronous coexistence of GIST and lung cancer has only rarely been reported. We report the case of a 65-year-old male, a former smoker, who was diagnosed with synchronous occurrence of mesenteric GIST and Primary Large Cell Neuroendocrine Cancer (LCNEC) of the lung. There are few case reports on synchronous occurrence of GIST with primary lung cancer but till date no case report exists on GIST with primary LCNEC of lung.

First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study.

The BRIGHT study ( ClinicalTrials.gov identifier: NCT00877006) was initiated to compare the efficacy and safety of bendamustine plus rituximab (BR) with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) for treatment-naive patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma. This publication provides long-term follow-up data. Patients were monitored for a minimum of 5 years after completion of study treatment for the time-to-event end points of progression-free survival (PFS), event-free survival, duration of response, and overall survival per investigator assessment. Data on the number of patients who received second-line anticancer treatment and the occurrence of other malignancies were also collected. The medians were not reached for any of the time-to event end points for either the BR or R-CHOP/R-CVP study treatment groups by study completion. PFS rates at 5 years were 65.5% in the BR treatment group and 55.8% in the R-CHOP/R-CVP group. The difference in PFS was considered significant with a hazard ratio of 0.61 (95% CI, 0.45 to 0.85; P = .0025). The hazard ratio for event-free survival and duration of response (P = .0020 and .0134, respectively) also favored the BR regimen over R-CHOP/R-CVP. However, no significant difference in overall survival was observed. The overall safety profiles of BR, R-CHOP, and R-CVP were as expected; no new safety data were collected during long-term follow-up. A higher number of secondary malignancies was noted in the BR treatment group. Overall, BR demonstrated better long-term disease control than R-CHOP/R-CVP and should be considered as a first-line treatment option for patients with indolent and mantle-cell lymphoma.

Does Occurrence of Other Malignancy After Essential Thrombocythemia and Polycythemia Vera Influence their Rate of Transformation to Myelofibrosis?

Introduction: Other malignancies (OM) were reported to be increased in patients with essential thrombocythemia and polycythemia vera PV. However, the effect of coexistent OM on the rate of disease transformation to myelofibrosis is unknown. Objective: To determine the occurrence of OM in patients with ET and PV and their influence on transformation rate to overt MF. Methods: Fisher's exact test, and Mann-Whitney test were used to compare categorical and continuous variable, respectively. Control group without OM matched for age, MPN diagnosis type and year was created to compare transformation rates, expressed by Kaplan-Meier curve and Log rank test. Results: We perform a retrospective chart review for 783 patients referred to our institution between years 1960 - 2013 with diagnosis of Philadelphia-negative myeloproliferative neoplasm of which 256 had ET, 165 PV and 362 post ET- or post PV- MF. Overall, 107 (13.7%) patients had OM prior to MF transformation, accounting for total of 125 cases. See table for OM types and distribution. In total, 9 patients had more than 1 OM with the most common being prostatic carcinoma (n=6), melanoma (n=4) and renal cell carcinoma (n=2). Relapsed/refractory OM were noticed in 15 patients, 3 of these had recurrence only prior MPN. None of alive patients with refractory OM experienced progression after MF transformation. Median age at diagnosis of MPN and OM (59 and 62 years), median age at the time of first event (OM or MPN; 51 and 53 years), and male to female ratio (1:1) were similar. Time to secondary OM was shorter than time to secondary MPN (6.5 vs 9 years, p>0.05). After median follow up of 30 months (range, 1-150), 49 (46%) patients had died. Eleven (23%) patients died because of OM progression, most commonly due to lung carcinoma and melanoma. No MPN related deaths were observed, however, 2 patients progressed to acute leukemia. Median overall survival OS for MPN was 160 months (range, 1-240) and was not different for patients with and without MF (212 and 173 months; p>0.05). No significant differences were detected between patients with and without MF in terms of age at the time of MPN diagnosis, gender, MPN characteristics (cytogenetic, molecular mutations) or time between OM and MPN. However, patients who transformed to MF were older at the time of OM (53 vs 59 years, p= 0.041, 95% CI: 1.2-11.7). Similarly, within a group of MF, patients with OM prior to MPN were younger at the time of OM (53 vs 62 years, p 0.05, chi square 1.14). However, patients who developed OM after MPN had longer time to transformation (14 years, range 1-36, p=0.011, HR 1.9, 95%CI of 1.3 -4.4), which remained significant when control group was added, p=0.024 [Fig.] Conclusions: OM diagnosed after ET or PV does not seem to influence rate of disease transformation to MF. | | ET/PV, n=421 | ET/PV -> MF, n= 362 | | ----------------------- | --------------- | ------------------- | --------------- | | OM characteristics | OM prior MPN, n | OM after MPN, n | OM prior MPN, n | OM after MPN, n | | No. of patients with OM | 29 | 26 | 19 | 33 | | No. of OM | 30 | 26 | 26 | 43 | | Breast | 5 | 4 ( 1*) | 2 (1*) | 3 | | Female reproductive | 5 | | 1 | 4 | | Prostate | 7 | 1 | 6 (1*) | 14 (1*) | | Gastrointestinal tract | 2 | 4 | 6 | 3 | | Genitourinary tract | | 3 (1*) | 4 | 2 | | Lungs | 1 | 3 (3*) | | | | Melanoma | 3 (1*) | 2 | 4 | 9 (1*) | | Soft tissue | 1 | 2 (1*) | 1 | | | Thyroid | 3 | 2 (1*) | 1 | 2 | | Head and neck | 1 (1*) | | | | | Hematologic malignancy | 3 | 5 (1*) | | 6 (1*) | * (*) stands for relapsed or refractory disease Table. ![Figure][1] Disclosures Pemmaraju: Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Cortes: Pfizer: Consultancy, Research Funding; Teva: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding. [1]: pending:yes

Second primary malignancies in renal cortical neoplasms: an updated evaluation from a single institution.

To examine the incidence of secondary primary malignancies in patients with renal cortical neoplasms. Between January 1989 and July 2010, 3647 patients underwent surgery at our institution for a renal cortical neoplasm and were followed through 2012. Occurrence of other malignancies was classified as antecedent, synchronous, or subsequent. All patients with antecedent malignancies (n=498) and a randomly selected half of those with synchronous malignancies (n=83) were excluded. The expected number of second primaries was calculated by multiplying Surveillance, Epidemiology, and End Results Program incidence rates of renal cortical neoplasms by person-years at risk within categories of age, sex, and year of diagnosis. The standardized incidence ratio (SIR) was calculated as observed cancers divided by expected incidence of the cancer, with approximation to the exact Poisson test used to obtain confidence intervals (CI) and p values. Of 3066 patients with renal cortical neoplasms, 267 had a second primary cancer; the five most common in men were prostate, colorectal, bladder, lung, and non-Hodgkin's lymphoma; the five most common in women were breast, colorectal, lung, endometrium, and thyroid. Men demonstrated higher than expected thyroid cancer rate (SIR 5.0; 95% CI 1.83-10.88, p=0.002), and women had higher than expected rates of stomach cancer (SIR 5.0; 95% CI 1.61-11.67, p=0.004) and thyroid cancer (SIR 4.62; 95% CI 1.69-10.05, p=0.003). The incidence of certain types of second malignancies may be higher in patients after diagnosis of renal cortical neoplasms compared to the general population. These observations can inform clinical follow-up in kidney cancer survivorship and future research studies.

Does Occurrence of Other Malignancy after Essential Thrombocythemia and Polycythemia Vera Influence Their Rate of Transformation to Myelofibrosis?

Introduction: Other malignancies (OM) were reported to be increased in patients with essential thrombocythemia "ET" and polycythemia vera "PV". However, the effect of coexistent OM on the rate of disease transformation to myelofibrosis "MF" is unknown.Objective: To determine the occurrence of OM in patients with ET and PV and their influence on transformation rate to overt MF.Methods: Fisher's exact test, and Mann-Whitney test were used to compare categorical and continuous variable, respectively. Control group without OM matched for age, MPN diagnosis type and year was created to compare transformation rates, expressed by Kaplan-Meier curve and Log rank test.Results: We perform a retrospective chart review for 783 patients referred to our institution between years 1960 - 2013 with diagnosis of Philadelphia-negative myeloproliferative neoplasm "MPN", of which 256 had ET, 165 PV and 362 post ET- or post PV- MF. Overall, 107 (13.7%) patients had OM prior to MF transformation, accounting for total of 125 cases. See table for OM types and distribution. In total, 9 patients had more than 1 OM with the most common being prostatic carcinoma (n=6), melanoma (n=4) and renal cell carcinoma (n=2). Relapsed/refractory OM were noticed in 15 patients, 3 of these had recurrence only prior MPN. None of alive patients with refractory OM experienced progression after MF transformation. Median age at diagnosis of MPN and OM (59 and 62 years), median age at the time of first event (OM or MPN; 51 and 53 years), and male to female ratio (1:1) were similar. Time to secondary OM was shorter than time to secondary MPN (6.5 vs 9 years, p>0.05). After median follow up of 30 months (range, 1-150), 49 (46%) patients had died. Eleven (23%) patients died because of OM progression, most commonly due to lung carcinoma and melanoma. No MPN related deaths were observed, however, 2 patients progressed to acute leukemia. Median overall survival "OS" for MPN was 160 months (range, 1-240) and was not different for patients with and without MF (212 and 173 months; p>0.05). No significant differences were detected between patients with and without MF in terms of age at the time of MPN diagnosis, gender, MPN characteristics (cytogenetic, molecular mutations) or time between OM and MPN. However, patients who transformed to MF were older at the time of OM (53 vs 59 years, p= 0.041, 95% CI: 1.2-11.7). Similarly, within a group of MF, patients with OM prior to MPN were younger at the time of OM (53 vs 62 years, p<0.001, 95%CI 5.0-23.5) and older at the time of MPN (67 vs 55 years, p=0.001, 95%CI 8.3-19.4) that patients who had OM after previous MPN. Overall time to transformation to MF was similar between ET and PV, and between studied cohort and control group (6 years, range 0.5-29, p>0.05, chi square 1.14). However, patients who developed OM after MPN had longer time to transformation (14 years, range 1-36, p=0.011, HR 1.9, 95%CI of 1.3 -4.4), which remained significant when control group was added, p=0.024 [Fig.]Conclusions: OM diagnosed after ET or PV does not seem to influence rate of disease transformation to MF.TableET/PV, n=421ET/PV -> MF, n= 362OM characteristicsOM prior MPN, nOM after MPN, nOM prior MPN, nOM after MPN, nNo. of patients with OM29261933No. of OM30262643Breast54 ( 1*)2 (1*)3Female reproductive514Prostate716 (1*)14 (1*)Gastrointestinal tract2463Genitourinary tract3 (1*)42Lungs13 (3*)Melanoma3 (1*)249 (1*)Soft tissue12 (1*)1Thyroid32 (1*)12Head and neck1 (1*)Hematologic malignancy35 (1*)6 (1*)(*) stands for relapsed or refractory disease [Display omitted] DisclosuresPemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Cortes:Pfizer: Consultancy, Research Funding; Teva: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding.

Occurrence of Malignant Tumours in the Acute Hepatic Porphyrias.

The porphyrias are a group of inherited metabolic diseases resulting from enzymatic deficiencies of specific haem biosynthetic enzymes. They can be classified as primarily acute and non-acute types. Clinically, the acute hepatic porphyrias (AHPs) are characterised by acute neurovisceral attacks. Patients with AHP may be at increased risk for development of hepatocellular carcinoma (HCC). However, systematic studies on the occurrence of other malignancies in patients with the AHPs have not been performed to date. Here, we studied the development of HCC and distinct malignant tumours in patients with the AHPs registered in a single European porphyria specialist centre. A questionnaire was designed and sent to all individuals (n = 122) diagnosed between 1970 and 2012 of whom a valid address was available (n = 82), requesting information on their personal and family history of cancer. Statistical analysis was performed to calculate incidence, prevalence and relative risk of HCC. To calculate confidence intervals, a Poisson distribution was assumed. Forty-nine patients (59.8%) returned a completed questionnaire. Overall, HCC was diagnosed in one female (2.1%), and the remaining patients reported on six distinct malignancies. We were able to confirm that HCC is an important complication in AHP. The patients in our cohort had an approximately 35-fold increased risk of developing HCC, similar to observations in other European countries. In addition, we detected colon, breast, uterine and thyroid cancer as well as lymphoma and a liver metastasis in patients with AHP. However, considering the small number of tumours and patients studied here, the data should be interpreted with caution, and further studies on cancer occurrence in AHP patients will require a multicentre setting.

Carcinogenic Wind Blows Through the Pipe: Rare Carcinoma of Trachea as Primary or Secondary Neoplasm

Carcinogenic Wind Blows Through the Pipe: Rare Carcinoma of Trachea as Primary or Secondary Neoplasm

Synchronous Gastrointestinal Stromal Tumor and Primary Lung Adenocarcinoma

Although rare, gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. The asynchronous occurrence of other malignancies in patients with GIST during the clinical course is relatively common. However, the synchronous coexistence of GIST and lung cancer has only rarely been reported. We experienced a case of coincidental primary lung adenocarcinoma and intestinal GIST. The present case is not only of interest due to the rare coincidence of GIST and lung cancer, but also because there was an epidermal growth factor receptor gene mutation in the lung cancer and a c-kit mutation in the GIST.

Acinic Cell Carcinoma of Minor Salivary Glands: A Clinicopathologic Study of 21 Cases

Acinic cell carcinoma (ACC) is an infrequent type of malignant salivary gland tumor. Approximately 16% of all ACCs occur in the mouth according to several small studies. This study was undertaken to 1) report on the clinicopathologic characteristics of 21 intraoral examples, 2) reconfirm the reported indolent behavior of these tumors, and 3) verify the synchronous or metachronous occurrence of other malignancies with ACC. Twenty-one patients with intraoral ACC were identified in the previous 27 years. Demographic data and histomorphologic characteristics were evaluated and follow-up information was sought. Fifteen patients (68%) were male and 6 female. Seven cases (33.3%) occurred in the buccal mucosa, 6 in the palate (28.6%), 5 involved the upper lip (23.8%), 2 the retromolar mucosa (9.5%), and 1 the lower lip (4.8%). The mean age of patients was 50 years, with the youngest being 13 and the oldest 73. The duration was known in 9 patients and varied from 4 months to longer than 15 years. The size of the tumors varied from 0.6 to 1.6 cm. Where reported, lesions were asymptomatic. Histologically, different patterns that included microcystic, papillary cystic, follicular and solid, and combinations of these types characterized the lesions. Follow-up information was obtained in 12 patients. Eleven patients did not report recurrence or metastatic disease. The follow-up extended from 10 months to 17 years. One patient had 2 recurrences due to erroneous diagnosis that led to inappropriate treatment. After properly diagnosed and treated, this patient has been free of tumor for 4 years. Of interest were the metachronous occurrence of lymphoma in 1 patient and the synchronous occurrence of renal cell carcinoma in another. This study confirms the indolent behavior of ACC of minor salivary glands and previous reports on the occasional synchronous or metachronous association of malignant salivary gland tumors with other malignancies.

Occurrence of other malignancies in patients with gastrointestinal stromal tumors

Almost one-third of gastrointestinal stromal tumors (GISTs) are discovered incidentally during investigative or therapeutic procedures for unrelated diseases. In this regard, GISTs may coexist with different types of cancer, either synchronously or metachronously. The frequency of this association and the spectrum of neoplasms involved have not been sufficiently analyzed. We conducted a review of the literature and our own records for cases with sporadic GISTs and other malignancies, with emphasis on solid tumors. Neurofibromatosis 1 and Carney triad-associated tumors were excluded. Based on these data, there were 518 cancers in 486 GIST patients among 4813 cases with informative data. The overall frequency of second tumors in different series varied from 4.5% to 33% (mean, 13%). A total of 29 patients had multiple malignancies. GISTs of gastric location were most commonly involved with other neoplasms, reflecting their overall high frequency (60%) of all GISTs. The major types of GIST-associated cancers were gastrointestinal carcinomas (n=228; 47%), lymphoma/leukemia, (n=36; 7%), and carcinomas of prostate (n=43; 9%), breast (n=34; 7%), kidney (n=27; 6%), lung (n=26; 5%), female genital tract (n=25; 5%), and carcinoid tumors (n=13; 3%). Other cancers included soft tissue and bone sarcomas (n=15; 3%), malignant melanoma (n=12; 2%), and seminoma (n=6; 1%). Occurrence of collision tumors and metastases of carcinoma or sarcoma into a GIST (the latter noted in 4 cases) can be challenging diagnostic problems. The potential nonrandom association and causal relationship between GIST and other neoplasms remain to be investigated.

Neuroendocrine tumors of the gastrointestinal tract (NETGI) and second primary malignancies--which is dominant?

13-46% of all patients with a neuroendocrine tumor of the gastrointestinal tract (NETGI, "Carcinoid") develop a carcinoma. The goal of our study was to find out the frequency of other malignancies in our patients with an NETGI and to discover which of the tumors was decisive for the clinical course. We documented the clinical findings in 55 patients with an NETGI who underwent surgery in our hospital, noted the occurrence of other malignancies and recorded a current follow-up. 13 of 55 patients (24%) had an additional carcinoma after a median follow-up of 53 months. In 11 of the 13 patients the NETGI was identified accidentally. None of them had developed the carcinoma after the NETGI. In most of our patients (11 out of 13) the carcinoma was clinically predominant and discovered before the NETGI. Thus, a special follow-up looking for a carcinoma is probably not mandatory after the diagnosis of an NETGI.

Occurrence of other malignancies in 1973 patients with basal cell carcinoma

To evaluate the possible association of other malignancies with basal cell carcinoma, we reviewed 1973 consecutive patients with basal cell carcinoma. We searched the Swedish Cancer Registry for records reporting malignancies in the study population (1958-1984) and the expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data. In 452 patients with basal cell carcinoma another malignancy was diagnosed. The expected number was 323 (relative risk = 1.4; 95% confidence interval = 1.3 to 1.5). A significant association with basal cell carcinoma was found in four cancer types for men and in three for women. For skin malignancies other than malignant melanoma there was more than a sixfold increased risk for men (relative risk = 6.8; 95% confidence interval = 4.8 to 9.4) and more than a threefold increased risk for women (relative risk = 3.1; 95% confidence interval = 1.4 to 5.9) during the period after the diagnosis of basal cell carcinoma. During the period before the diagnosis of basal cell carcinoma, there were also increased risks (men: relative risk = 5.0; 95% confidence interval = 3.1 to 7.5; women: relative risk = 4.0; 95% confidence interval = 1.9 to 7.4). This was in contrast to the risks of malignant melanoma. Before the diagnosis of basal cell carcinoma there was no significant increased risk of malignant melanoma but after the diagnosis there was more than a sixfold increased risk for men (relative risk = 6.8; 95% confidence interval = 4.8 to 9.4) and more than a fourfold increased risk for women (relative risk = 4.2; 95% confidence interval = 1.5 to 9.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Occurrence of other malignancies in patients treated for basal cell carcinoma of the skin. A cohort study.

The patient with basal cell carcinoma of the skin has sometimes been thought to run an increased risk for developing other malignancies. A retrospective cohort study of 468 cases including about 4 400 person-years of observation did not reveal a significant deviation from expected values estimated either from cancer register data or from cancer incidence in matched controls.

Lithium and pregnancy. I. Report from the Register of Lithium Babies.

We have collected information about 118 children born to mothers who were given lithium treatment during the first trimester of pregnancy. The data show that the risk of teratogenic effects is lower than one might have expected from some of the studies carried out on rats and mice; they do not answer the question of whether or not lithium is teratogenic in man. The data were collected retrospectively and therefore overestimate rather than underestimate the risk of teratogenicity.