Long-Term and Late Effects of Germ Cell Testicular Cancer Treatment and Implications for Follow-Up

2012 ◽  
Vol 30 (30) ◽  
pp. 3752-3763 ◽  
Author(s):  
Hege S. Haugnes ◽  
George J. Bosl ◽  
Hink Boer ◽  
Jourik A. Gietema ◽  
Marianne Brydøy ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Testicular Cancer ◽  
Germ Cell ◽  
Late Effects ◽  
Current Status ◽  
Malignant Neoplasms ◽  
Treatment Type ◽  
Increased Risk

Germ cell testicular cancer (TC) represents a malignancy with high cure rates. Since the introduction of cisplatin-based chemotherapy in the late 1970s, the 5-year survival rate has increased considerably, and it is currently above 95%. Because TC is usually diagnosed before the age of 40 years, these men can expect to live for another 40 to 50 years after being successfully treated. This success, however, is hampered by an increased risk of long-term and late effects of treatment. Secondary malignant neoplasms and cardiovascular disease represent the most common potentially life-threatening late effects, typically occurring more than 10 years after treatment. Other long-term effects include pulmonary toxicity, nephrotoxicity, neurotoxicity, decreased fertility, hypogonadism, and psychosocial problems. The incidence and time to onset of these various adverse effects vary according to treatment type and intensity. There is still little knowledge about underlying mechanisms and genetic susceptibility of the various adverse effects. Apart from treatment burden, it is not yet possible to identify patients who are at high risk for certain late effects after TC treatment. In this clinical review, we present the current status regarding different somatic and psychosocial long-term late effects after treatment for TC, based on Medline searches and our own research. Moreover, we postulate recommendations for general medical evaluations that should begin after treatment is completed and continue during follow-up.

Prevalence of childhood growth hormone deficiency in survivors of pediatric intracranial germ cell tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22526-e22526
Author(s):  
Diana Lone ◽  
Karim Thomas Sadak ◽  
Bradley S Miller ◽  
Michelle Roesler ◽  
Jenny N Poynter
Keyword(s):  
Growth Hormone ◽  
Germ Cell ◽  
Growth Hormone Deficiency ◽  
Late Effects ◽  
Germ Cell Tumors ◽  
Hormone Deficiency ◽  
Endocrine Disorders ◽  
Intracranial Germ Cell Tumors

e22526 Background: Survival rates for childhood cancer continue to rise, and there are now greater than 420,000 survivors in the United States. However, high cure rates come at the cost of short and long-term treatment-related toxicities. Endocrine disorders are among the most common late effects and are associated with poor health outcomes and lower quality of life. Survivors of pediatric intracranial germ cell tumors (iGCTs) are at high risk for endocrine disorders, particularly for growth hormone deficiency (GHD), due to their exposures to cranial radiation, chemotherapy, and brain surgery. To date, no long-term follow-up studies have explored the late effects experienced by survivors of iGCTs. Methods: Study participants were enrolled in the Germ Cell Tumor Epidemiology Study, which is a case-parent triad study conducted using the resources of the Children’s Oncology Group’s Childhood Cancer Research Network. Eligibility criteria included diagnosis with a germ cell tumor in any location at age 0-19 years in the years 2008-2015. The study population included 233 cases with a diagnosis of iGCT. We are currently following the cohort to evaluate outcomes and late effects of treatment, including medical record review to extract data on treatment characteristics and hormone deficiencies. This interim analysis includes chart review for 57 iGCT cases. Results: Of the 57 cases reviewed, there was a male predominance (73.7%) with the highest prevalence in non-Hispanic whites (80.4%). Cases of iGCTs can be subdivided into two main histologic subtypes, germinomas (36 cases) and non-germinomatous GCTs (NGGCT, 21 cases). The median age at diagnosis was 14.6 years for the germinomas and 10.5 years for NGGCTs. Data on growth hormone deficiency (GHD) was available for 42 of the 57 cases with a median follow-up of 7.4 years. Twenty-eight of the 42 cases (66.7%) had GHD; 19 in the germinoma group and 9 in the NGGCT group (p = 0.47). 17 of those with GHD were males (p = 0.10). There was no significant difference in prevalence of GHD by age of tumor diagnosis (p = 0.20). Conclusions: Survivors of iGCTs are at high risk for growth hormone deficiency. Identifying specific risk factors for developing GHD amongst these survivors can enhance the current guidelines for screening and management.

scholarly journals Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Chunkit Fung ◽  
Paul Dinh ◽  
Shirin Ardeshir-Rouhani-Fard ◽  
Kerry Schaffer ◽  
Sophie D. Fossa ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Testicular Cancer ◽  
Cancer Survivors ◽  
Current Status ◽  
Malignant Neoplasms ◽  
Targeted Prevention ◽  
Care Providers ◽  
National Guidelines ◽  
Testicular Cancer Survivors

Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects. Other long-term adverse outcomes include neuro- and ototoxicity, pulmonary complications, nephrotoxicity, hypogonadism, infertility, and avascular necrosis. Future research efforts should focus on delineation of the genetic underpinning of these long-term toxicities to understand their biologic basis and etiopathogenetic pathways, with the goal of developing targeted prevention and intervention strategies to optimize risk-based care and minimize chronic morbidities. In the interim, health care providers should advise TCS to adhere to national guidelines for the management of cardiovascular disease risk factors, as well as to adopt behaviors consistent with a healthy lifestyle, including smoking cessation, a balanced diet, and a moderate to vigorous intensity exercise program. TCS should also follow national guidelines for cancer screening as currently applied to the general population.

Long-term effects on renal function and blood pressure of treatment with cisplatin, vinblastine, and bleomycin in patients with germ cell cancer.

1988 ◽  
Vol 6 (11) ◽  
pp. 1728-1731 ◽  
Author(s):  
S W Hansen ◽  
S Groth ◽  
G Daugaard ◽  
N Rossing ◽  
M Rørth
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Cancer ◽  
Long Term Effects ◽  
Increased Risk ◽  
The Mean

Long-term effects of cisplatin on renal function were investigated in 34 patients with germ cell cancer observed for a median of 65 months (range, 43 to 97 months). All patients achieved a complete remission after treatment with cisplatin (median dose 583 mg/m2), vinblastine, and bleomycin. None of the patients relapsed during follow-up. During treatment the glomerular filtration rate (GFR) decreased by 18% (P less than .05). During follow-up kidney function recovered in ten patients and partly improved in eight patients. Changes in plasma creatinine did not consistently correspond to alterations in GFR. The mean increase in systolic blood pressure during follow-up did not differ from the increase seen in a group of age-matched healthy men. The mean increase in diastolic pressure, however, was significant (P less than .05), but was entirely due to hypertension observed in six patients. Renography of these patients was normal. We conclude that the decrease in GFR observed during treatment with cisplatin is partly reversible. Cisplatin-treated patients have an increased risk of developing hypertension years after treatment.

Association of long-term exposure to circulating platinum with adverse late effects in testicular cancer survivors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4528-4528
Author(s):  
Hink Boer ◽  
Johannes H Proost ◽  
Janine Nuver ◽  
Sophie Bunskoek ◽  
Joyce Q. Gietema ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Late Effects ◽  
Compartment Model ◽  
Population Pharmacokinetic ◽  
Serum Samples ◽  
Time Points ◽  
Two Compartment Model ◽  
Testicular Cancer Survivors

4528 Background: Successful platinum(Pt)-based chemotherapy for testicular cancer (TC) comes at the price of late cardiovascular morbidity and neurotoxicity. Damage induced by circulating Pt could be an etiological mechanism. We investigated the relation between circulating Pt and late effects. Methods: In 96 consecutive TC patients (med age 29 [17-53] at chemotherapy), 3 serum samples and a 24h-urine sample were collected on several time-points med 5 yrs (1-13) after treatment. Pt concentrations ([Pt]) were measured with a sensitive voltammetric method (Lancet 2000, 355:1075). Measured [Pt] combined with cisplatin dose, age, weight and height were analyzed simultaneously to construct a population pharmacokinetic (PK) model using NONMEM. Based on the PK parameters of each patient, individual [Pt] at 1, 3, 5, 10 yrs after start and AUC were calculated. Cardiovascular status, paresthesia and markers of vascular damage were assessed after a med follow-up (FU) of 9 yrs (3-15). Results: Decay of [Pt] was best described by a two compartment model. Mean terminal T1/2 was 3.7 (±0.3) yrs. At all time-points [Pt] correlated with cisplatin dose and renal function during treatment. [Pt] at 3 yrs correlated with systolic blood pressure (BP) (r=.32, p<0.01) and creatinine clearance (CRCL) (r=-.25, p=0.02) at FU. Patients with increased BP had higher Pt AUCs than patients with normal BP (table). Pt AUCs were higher in patients with paresthesia (table). Conclusions: Known late effects of cisplatin-based chemotherapy such as hypertension and paresthesia are related to higher circulating [Pt]. Long-term exposure to Pt is involved in healthy tissue damage in TC survivors. [Table: see text]

scholarly journals Long-term follow-up of retinoblastoma survivors: Experience from India

2017 ◽  
Vol 06 (04) ◽  
pp. 176-179 ◽  
Author(s):  
Rachna Seth ◽  
Amitabh Singh ◽  
Vijay Guru ◽  
Bhavna Chawla ◽  
Sushmita Pathy ◽  
...  
Keyword(s):  
Late Effects ◽  
Healthy Lifestyle ◽  
Second Neoplasms ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Unilateral Disease ◽  
Contracted Socket ◽  
After Cancer

Abstract Background: Retinoblastoma (Rb) is the most common primary intraocular tumor of infancy and childhood. Survivors' ocular and visual problems and increased risk for subsequent malignancy are well documented, but data on long-term health status of Rb survivors are limited, this being particularly true for India. Methodology: Children who had completed treatment for Rb at least 2 years ago before and were under follow-up at the after cancer treatment clinic were evaluated. Results: In our series of 213 patients, the median age was 29 months, there was a male preponderance, and majority had unilateral disease. Enucleation was done in almost three-fourth and 3% underwent bilateral enucleation. Majority of the patients received chemotherapy, and few received radiation. Growth was affected in about one-third and majority were those who had received radiation. Diminished vision was noticed in about one-sixth. Orbital hypoplasia and contracted socket were seen in 14.1% cases. 2.7% were hearing impaired. About one-sixth had a global intelligence delay. Second neoplasms were seen in 0.01%. No other abnormalities were seen. Conclusions: Common late effects in our Rb survivors include diminished vision in the salvage eye, intellectual disability, and contracted socket; there is a need for timely institution of prosthesis to avoid late effects such as hypoplasia, contracted sockets, and better cosmesis and enhanced self-esteem. Second neoplasm is a concern. Lifelong follow-up and counseling of a healthy lifestyle are needed for Rb survivors.

scholarly journals Current survivorship recommendations for patients with Hodgkin lymphoma: focus on late effects

Blood ◽  
2014 ◽  
Vol 124 (23) ◽  
pp. 3373-3379 ◽  
Author(s):  
Andrea K. Ng
Keyword(s):  
Hodgkin Lymphoma ◽  
Late Effects ◽  
Malignant Neoplasm ◽  
Late Complications ◽  
Current Evidence ◽  
Future Research ◽  
Increased Risk ◽  
Reduction Strategies

AbstractLong-term survivors of Hodgkin lymphoma (HL) are at an increased risk for a range of late complications, with subsequent malignant neoplasm and cardiovascular disease representing the 2 leading causes of death in these patients. Raising awareness, close follow-up, and adoption of selected early-detection and risk-reduction strategies may help to reduce the adverse impact of these late effects on patients. This chapter reviews known long-term complications of HL therapy, risk factors, and the timing of their occurrence. Where available, data on the efficacy of screening for selected late effects of HL are presented. Current evidence-based and consensus-based recommendations on follow-up of long-term HL survivors are also reviewed. As HL therapy evolves over time, late effects and implications on follow-up of patients treated in the contemporary era should be considered and opportunities for future research should be explored.

scholarly journals Current survivorship recommendations for patients with Hodgkin lymphoma: focus on late effects

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 488-494 ◽  
Author(s):  
Andrea K. Ng
Keyword(s):  
Hodgkin Lymphoma ◽  
Late Effects ◽  
Malignant Neoplasm ◽  
Late Complications ◽  
Current Evidence ◽  
Future Research ◽  
Increased Risk ◽  
Reduction Strategies

AbstractLong-term survivors of Hodgkin lymphoma (HL) are at an increased risk for a range of late complications, with subsequent malignant neoplasm and cardiovascular disease representing the 2 leading causes of death in these patients. Raising awareness, close follow-up, and adoption of selected early-detection and risk-reduction strategies may help to reduce the adverse impact of these late effects on patients. This chapter reviews known long-term complications of HL therapy, risk factors, and the timing of their occurrence. Where available, data on the efficacy of screening for selected late effects of HL are presented. Current evidence-based and consensus-based recommendations on follow-up of long-term HL survivors are also reviewed. As HL therapy evolves over time, late effects and implications on follow-up of patients treated in the contemporary era should be considered and opportunities for future research should be explored.

scholarly journals Second Malignant Neoplasms (SMN) in Myeloma Patients Post Stem Cell Transplant (SCT)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1839-1839
Author(s):  
Samar Kulkarni ◽  
John Murray ◽  
Jim Cavet ◽  
Mike Dennis ◽  
Adrian Bloor ◽  
...  
Keyword(s):  
Stem Cell ◽  
Solid Tumours ◽  
Malignant Neoplasms ◽  
High Dose ◽  
Cell Transplant ◽  
Treatment Needs ◽  
Increased Risk ◽  
Long Term Consequences

Abstract Introduction: Recent developments in management of patients with myeloma have resulted in longer survival. Availability of newer class of agents for treatment has prolonged survival, improved quality of life and achieved better disease control. Use of SCT, either autologous (AutoSCT) and to a lesser extent allogeneic (AlloSCT) still forms an important aspect of myeloma treatment pathway. Improved survivorship mandates evaluation of long term consequences and risk of SMN is one of the most important long-term consequences affecting overall outcome. Aim: Estimate the risk of SMN post SCT in patients with Myeloma. Methods and Materials: Analysis includes 779 patients who received SCT for myeloma from January 2002 to December 2019. Data was collected using case records, electronic patient records, transplant database and information from referring hospitals. Follow-up was updated to June 2020. Results: Analysis includes 779 patients with myeloma (M: 488, F:291; median age:59yr, range: 26-75) receiving AutoSCT (n=716) or AlloSCT (n=63). Conditioning for AutoSCT was high dose melphalan in majority (n=714, 99.7%). AlloSCT conditioning was RIC (n=40/63, 63.5%) or MAC (n=23/63, 36.5%). TBI was part of conditioning in 51/779 (6.5%). There was no difference in demographics between two groups. Results: Median follow-up was 46 mo (range: 0.2-220). Second malignancy was identified in 48 of 779 cases (6.0%). SMN developed in 6/63 (10%) AlloSCT and 42/716 (6%) AutoSCT patents (p=0.25). SMN types were haematological (n=21), lymphoma (n=6) and solid tumours (n=21). MDS was the only haematological SMN in this series. Secondary MDS developed in 20/21 of AutoSCT as compared to 1/63 in AlloSCT (p=0.01). Non-haematological SMN were breast (n=3), upper GI (n=3), lower GI (n=2), hepato-billiary (n=2), prostate (n=3), skin (n=5), and unknown primary (n=1). SMN incidence was higher with increasing follow-up (2002-2014, 8%; 2015-2017, 2.8%, 2018-2019, 0%, p=0.002). There was no association with development of SMN and gender, age at transplant, type of stem cell source or transplant conditioning. Incidence of SMN was significantly higher for all sites as compared to general population. Cumulative incidence of SMN was 5% at 5 yr, and 15% at 10 yr for AutoSCT patients. Conclusion: Myeloma patients are at increased risk of SMN and need monitoring for long term side effects. Development of MDS post AutoSCT is the commonest SMN post AutoSCT but there is increased incidence of solid tumours as well. Impact of new modalities of treatment needs long term monitoring. Disclosures Bloor: Novartis: Honoraria; Kite, a Gilead Company: Honoraria.

Estimated long-term outcomes in children newly diagnosed with standard risk acute lymphoblastic leukemia (ALL) based on similarly treated members of the childhood cancer survivor study (CCSS) cohort.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10032-10032
Author(s):  
Stefan Essig ◽  
Qiaozhi Li ◽  
Yan Chen ◽  
Johann Hitzler ◽  
Wendy M. Leisenring ◽  
...  
Keyword(s):  
Health Status ◽  
Late Effects ◽  
Chronic Condition ◽  
Health Conditions ◽  
Malignant Neoplasms ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Increased Risk ◽  
Standard Risk

10032 Background: Therapy for ALL has evolved such that the risk for late effects in children treated in early eras is likely different from those that will occur in children treated today. In order to estimate future risks for late effects in newly diagnosed children with standard risk ALL, we examined the long-term outcomes in a cohort of patients enrolled in the CCSS who were treated in a manner analogous to contemporary ALL therapies. Methods: We assessed outcomes that occurred ≥5 years from diagnosis in survivors of ALL enrolled in the CCSS who were aged 1-9.9 years at diagnosis, treated with 0-120 mg/m2 of anthracyclines and 0-1000 mg/m2 of alkylating agents, and no radiotherapy. We compared their risks for death, second malignant neoplasms (SMN), chronic physical health conditions and decreased health status with the general population (death and SMN) and the CCSS sibling cohort (remaining outcomes). Results: 556 survivors were eligible. At last assessment, they were a median of 27.8 years old (range 9.1 to 45.7) and 23.4 years (range 5.0-38.0) from diagnosis. 29/556 (5.2%) died (standardized mortality ratio 3.6, 95% CI 2.4-5.2); 12 of these deaths were due to ALL recurrence. Compared to siblings, the rate ratio for ≥1 chronic condition was 1.4 (95% CI 1.3-1.6), and for a severe/life threatening chronic condition was 1.7 (95% CI 1.3-2.3). Four survivors (0.7%) developed a SMN (standardized incidence ratio 1.7, 95% CI 0.5-4.5), 114 were obese (odds ratio (OR) 1.2, 95% CI 1.0-1.5), and 2 (0.4%) reported a stroke. No survivors reported symptomatic congestive heart failure. The OR for reporting adverse general health was 1.2 (95% CI 0.8-1.8), poor mental health 1.3 (95% CI 1.0-1.8), decreased functional status 2.1 (95% CI 1.4-3.0), and activity limitations 1.4 (95% CI 1.1-1.8). Conclusions: Children treated for standard risk ALL on contemporary protocols are at increased risk for future chronic health conditions and decreased health status. Despite excellent survival after leukemia therapy, such survivors will likely benefit from life-long medical care focused on the long-term risks stemming from their therapy.

Treatment-Specific Risks of Second Malignancies and Cardiovascular Disease in 5-Year Survivors of Testicular Cancer

2007 ◽  
Vol 25 (28) ◽  
pp. 4370-4378 ◽  
Author(s):  
Alexandra W. van den Belt-Dusebout ◽  
Ronald de Wit ◽  
Jourik A. Gietema ◽  
Simon Horenblas ◽  
Marieke W.J. Louwman ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Cox Regression ◽  
Late Complication ◽  
Late Complications ◽  
Malignant Neoplasms ◽  
Second Malignancies ◽  
Similar Extent ◽  
Second Malignant Neoplasms

Purpose To compare radiotherapy and chemotherapy effects on long-term risks of second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) in testicular cancer (TC) survivors. Patients and Methods In our nationwide cohort comprising 2,707 5-year TC survivors, incidences of SMNs and CVDs were compared with general-population rates by calculating standardized incidence ratios (SIRs) and absolute excess risks (AERs). Treatment effects on risks of SMN and CVD were quantified in multivariable Cox regression and competing risks analyses. Results After a median follow-up time of 17.6 years, 270 TC survivors developed SMNs. The SIR of SMN overall was 1.7 (95% CI, 1.5 to 1.9), with an AER of 32.3 excess occurrences per 10,000 person-years. SMN risk was 2.6-fold (95% CI, 1.7- to 4.0-fold) increased after subdiaphragmatic radiotherapy and 2.1-fold (95% CI, 1.4- to 3.1-fold) increased after chemotherapy, compared with surgery only. Subdiaphragmatic radiotherapy increased the risk of a major late complication (SMN or CVD) 1.8-fold (95% CI, 1.3- to 2.4-fold), chemotherapy increased the risk of a major late complication 1.9-fold (95% CI, 1.4- to 2.5-fold), and smoking increased the risk of a major late complication 1.7-fold (95% CI, 1.4- to 2.1-fold), compared with surgery only. The median survival time was 1.4 years after SMN and 4.7 years after CVD. Conclusion Radiotherapy and chemotherapy increased the risk of developing SMN or CVD to a similar extent as smoking. Subdiaphragmatic radiotherapy strongly increases the risk of SMNs but not of CVD, whereas chemotherapy increases the risks of both SMNs and CVDs. Prolonged follow-up after chemotherapy is needed to reliably compare the late complications of radiotherapy and chemotherapy after 20 years.

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