Nonmelanoma skin cancer in survivors of childhood and adolescent cancer: a report from the childhood cancer survivor study.

PURPOSE: Nonmelanoma skin cancer (NMSC) has become the most common type of cancer in many populations throughout the world. Ultraviolet and ionizing radiation are known risk factors. Because NMSCs are rarely lethal and most cancer registries do not routinely report data regarding these cancers, they have received little attention in studies evaluating long-term effects of cancer therapy. This article reports on the occurrence of secondary NMSC as a long-term effect of cancer therapy in survivors of childhood cancer. PATIENTS AND METHODS: The Childhood Cancer Survivor Study (CCSS) is a cohort study of 5-year survivors of childhood and adolescent cancer from 25 participating institutions in North America. NMSC patients were defined by a history of basal cell or squamous cell carcinoma of the skin after primary malignancy treatment. Demographic and treatment data were collected and analyzed. RESULTS: Among the 13,132 eligible CCSS participants, 213 have reported NMSC; 99 patients (46%) have had multiple occurrences. Median age of occurrence was 31 years (range, 7 to 46 years). Location of NMSC included head and neck (43%), back (24%), chest (22%), abdomen and pelvis (5%), extremity (3%), and unknown (4%). Ninety percent of patients had previously received radiation therapy (RT); 90% of tumors occurred within the RT field. RT was associated with a 6.3-fold increase in risk (95% CI, 3.5- to 11.3-fold). CONCLUSION: Long-term survivors of childhood and adolescent cancer who were treated with RT are at highest risk for developing NMSC. Educational efforts need to be directed to this population to facilitate early diagnosis of NMSC and reduction in sun exposure.     

Childbirth after adolescent and young adult cancer: a population-based study

Purpose

Annually, >?45,000 US women are diagnosed with cancer during adolescence and young adulthood (AYA). Since 2006, national guidelines have recommended fertility counseling for cancer patients. We examined childbirth after AYA cancer by calendar period, cancer diagnosis, and maternal characteristics.

Methods

We identified a cohort of women with an incident invasive AYA cancer diagnosis at ages 15–39 during 2000–2013 in North Carolina. Cancer records were linked with statewide birth certificates through 2014. Hazard ratios (HR) and 95% confidence intervals (CI) for first post-diagnosis live birth were calculated using Cox proportional hazards regression.

Results

Among 17,564 AYA cancer survivors, 1989 had ≥?1 birth after diagnosis during 98,397 person-years. The 5- and 10-year cumulative incidence of live birth after cancer was 10 and 15%, respectively. AYA survivors with a post-diagnosis birth were younger at diagnosis, had lower stage disease, and had less often received chemotherapy than those without a birth. The 5-year cumulative incidence of post-diagnosis birth was 10.0% for women diagnosed during 2007–2012, compared to 9.4% during 2000–2005 (HR?=?1.01; 0.91, 1.12), corresponding to periods before and after publication of American Society of Clinical Oncology fertility counseling guidelines in 2006.

Conclusions

Despite advances in fertility preservation options and recognition of fertility counseling as a part of high-quality cancer care, the incidence of post-diagnosis childbirth has remained stable over the last 15 years.

Implications for Cancer Survivors

Our study uses statewide data to provide recent, population-based estimates of how often AYA women have biological children after a cancer diagnosis.

     

Hospitalizations among children of survivors of childhood and adolescent cancer: a population-based cohort study

Curative but potentially mutagenic cancer therapy might lead to untoward disorders and increased hospitalization among the offspring of childhood cancer survivors. Hospitalizations in childhood were evaluated in a population-based cohort of 1,920 offspring of 3,963 childhood cancer survivors, 6,394 offspring of 5,657 siblings and 9,594 population-based comparisons. The Danish Cancer Registry, Central Population Register and National Hospital Register were used to identify study subjects and hospitalizations. The probability for children in the offspring cohorts of being hospitalized before a given age was estimated using the Kaplan-Meier method. Hospitalization rate ratios (HRRs) were calculated using a Cox proportional hazards model with population comparisons as referent. Little differences in hospitalization histories were seen among offspring in the 3 cohorts. HRRs of overall hospitalization was 1.05 (95% CI, 0.98-1.12) for offspring of survivors and 1.01 (95% CI, 0.97-1.05) for offspring of siblings, neither of which was significantly different from that of population comparisons. No significant associations were seen for most of the main diagnostic groups of diseases including infections and perinatal disorders. A 6-fold excess risk of hospitalization for malignant tumors in survivors' offspring, however, could largely be explained by hereditary cancer syndromes, and part of the 2-fold excess hospitalization for benign tumors might similarly be explained by an underlying genetic susceptibility or by increased surveillance of children born to survivors. Assuming that hospitalization is an indicator of multifactorial genetic disease, the findings provide further reassurance that cancer therapies do not confer a high risk of such conditions in offspring born after treatments.     

Pregnancy after adolescent and adult cancer: a population-based matched cohort study

Despite fertility-preserving initiatives, postcancer reproduction is expected to be lower than that of the general population. Using data from the Cancer Registry and the Medical Birth Registry of Norway, postcancer pregnancy rates were analyzed in 27,556 survivors and compared to those from a matched comparison group ("controls") from the general population. All were born after 1950, diagnosed from 1967 to 2004 at age of 16-45, and had an observation time from the date of diagnosis (assigned date for controls), until pregnancy, death, age 46, or December 31, 2006. Cox regression was used to estimate pregnancy rates, after adjusting for educational level, parity and diagnostic period. Overall, cancer survivors had a lower pregnancy rate than the controls, but the rate for survivors was higher in males than in females [hazard rate (HR)=0.74 (95% confidence interval (CI) 0.71-0.78) and HR=0.61 (95% CI 0.58-0.64), respectively]. However, the rates did not differ between controls and survivors of malignant melanoma or thyroid cancer. By contrast, the lowest HRs for pregnancy occurred in survivors of leukemia, cervical or breast cancer. Increased pregnancy rates during the study period were detected for ovarian cancer [HR=0.2 (95% CI 0.1-0.3) to HR=0.7 (95% CI 0.5-0.9)], testicular cancer [HR=0.6 (95% CI 0.4-0.9) to HR=0.8 (95% CI 0.7-0.8)], and Hodgkin lymphoma diagnosed in men [HR=0.7 (95% CI 0.5-0.9) to HR=0.9 (95% CI 0.7-1.0)]. In summary, fertility-preserving attempts have succeeded in patients with ovarian or testicular cancer and in males with Hodgkin lymphoma. Male survivors initiated pregnancies in a higher degree than female survivors.     

隐匿性乳腺癌的诊断和治疗

目的 探讨隐匿性乳腺癌的诊断、治疗及预后.方法 收集23例隐匿性乳腺癌患者的临床和随访资料,并进行分析.结果 23例患者均为女性,平均57.7岁.术前行影像学检查22例,其中行乳腺超声检查17例,8例发现可疑结节;行乳腺钼靶摄片9例,阳性3例;行乳腺MRI检查2例,1例发现异常钙化.20例行同侧乳腺癌改良根治术,16例进行化疗,4例放疗.随访期间,2例患者发生肺转移,其中1例多处转移.结论 术前排除其他部位原发癌的可能后,表现为腋窝淋巴结转移癌的患者即可诊断隐匿性乳腺癌.对隐匿性乳腺癌,乳腺必须进行治疗,可行乳腺癌改良根治术或腋窝淋巴结清扫+全乳放疗.     

Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study

BACKGROUND: The objective of the current study was to examine the risk factors for progression in severity of anthracycline-induced cardiac dysfunction, thereby providing information that is useful in refining cancer treatment regimes and guiding follow-up. METHODS: Serial echocardiograms were performed on 101 acute lymphoblastic leukemia survivors and 83 Wilms tumor survivors after a mean interval of 6.2 years and 6.7 years since last anthracycline dose, respectively, at first study, and after 10.3 years and 11.1 years, respectively, at second study. The paired data were contrasted with data from 100 normal subjects, and potential correlations with follow-up interval, cumulative dose, cancer diagnosis, gender, age at diagnosis, and growth were explored using univariate and multiple regression techniques. RESULTS: The most important predictor of worsening cardiac performance was total anthracycline dose. As a group, patients receiving < 240 mg/m(2) showed no deterioration of left ventricular end systolic stress at > 10 years from the end of treatment. CONCLUSIONS: Survivors who have received low-dose anthracycline require cardiac surveillance infrequently. In good prognosis tumors, cumulative anthracycline dose should be maintained at < 250 mg/m(2).     

Cholelithiasis after treatment for childhood cancer

The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8-54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones.     

Breast cancer developing after chemotherapy for osteosarcoma: a case report.

A 24-year-old patient who developed breast cancer 16 years after chemotherapy for osteosarcoma is presented. She had no family history of cancer. She had also not had radiotherapy. She had been given chemotherapy consisting of VAOMT (vincristine 10.2 mg, cyclophosphamide 900 mg, mitomycin C 15.2 mg, chromomycin A3 25.8 mg) pre- and post-operatively in the treatment of her osteosarcoma. Careful long-term follow-up is required after treatment of malignant neoplasms because there is a possibility of developing a second malignancy.     

Skin cancer in survivors of childhood and adolescent cancer

The incidence of basal cell carcinoma (BCC) has been related to ionizing radiation, particularly for exposure occurring at young age. In this study, we considered the incidence of second skin neoplasms in long-term survivors from childhood cancer. We considered second primary cancers occurring among 776 subjects (436 males, 340 females) with first primary cancer diagnosed before age 20 years, between 1974 and 2001, in the Swiss Cantons of Vaud and Neuchatel (786,000 inhabitants). Five BCC were observed versus 0.43 expected (standardized incidence ratio: 11.6, 95% confidence interval: 3.7-27.1). No case of cutaneous squamous cell carcinoma, nor of malignant melanoma was observed. The estimated radiation doses at 1mm through the skin ranged between 7 and 27 Sv. These data confirm that BCC are strongly related to ionizing radiation exposure in childhood. All the BCC were located within the radiation field, thus indicating that ionizing radiation is the key aetiological factor, even in the absence of any meaningful interaction with UV.     

Outcome after the introduction of a multimodality treatment program for locally advanced rectal cancer.

AIM: This prospective study reports the results of a multimodality treatment protocol in patients with locally advanced rectal cancer and assesses outcome after curative vs non-curative surgery and in relation to primary advanced vs locally recurrent cancer. METHODS: Between 1991 and 2002, 122 patients completed the protocol. Fifty-eight had primary advanced and sixty-four had locally recurrent rectal cancer. Median follow up was 82 months (5-143). RESULTS: A potentially curative resection was achieved in 59% of the patients with primary advanced and in 34% of patients with locally recurrent cancer. After curative resection, 53 and 59%, respectively, were free from recurrence during the observation time (median 82 months) and the overall 5-year survival was 34 and 40%. Overall 5-year survival in all patients with primary advanced cancer was 29 and 16% in all patients with locally recurrent rectal cancer. CONCLUSION: Multimodality treatment may cure at least a third of patients with locally advanced rectal cancer provided a radical resection is performed. As the post-operative morbidity is high, an optimised patient selection for neo-adjuvant treatment and surgery is essential. However, palliative surgery may benefit the patient if local control is achieved. Future studies should focus on the problem of distant metastasis.     

Fluoride exposure in public drinking water and childhood and adolescent osteosarcoma in Texas

Purpose

The purpose of this study was to examine the association between fluoride levels in public drinking water and childhood and adolescent osteosarcoma in Texas; to date, studies examining this relationship have been equivocal. Using areas with high and low naturally occurring fluoride, as well as areas with optimal fluoridation, we examined a wide range of fluoride levels in public drinking water.

Methods

This was a population-based case–control study, with both cases and controls obtained from the Texas Cancer Registry. Eligible cases were Texas children and adolescents <20 years old diagnosed with osteosarcoma between 1996 and 2006. Controls were sampled from children and adolescents diagnosed with either central nervous system (CNS) tumors or leukemia during the same time frame. Using geocoded patient addresses at the time of diagnosis, we estimated patients’ drinking water fluoride exposure levels based on the fluoride levels of their residence’s public water system (PWS). Unconditional logistic regression models were used to assess the association between osteosarcoma and public drinking water fluoride level, adjusting for several demographic risk factors.

Results

Three hundred and eight osteosarcoma cases, 598 leukemia controls, and 604 CNS tumor controls met selection criteria and were assigned a corresponding PWS fluoride level. PWS fluoride level was not associated with osteosarcoma, either in a univariable analysis or after adjusting for age, sex, race, and poverty index. Stratified analyses by sex were conducted; no association between PWS fluoride level and osteosarcoma was observed among either males or females.

Conclusions

No relationship was found between fluoride levels in public drinking water and childhood/adolescent osteosarcoma in Texas.

     

High grade surface osteosarcoma: a clinicopathologic study of 46 cases

BACKGROUND: High grade surface osteosarcoma is a rare subtype of osteosarcoma arising on the surface of bone, accounting for only 8.9% of surface osteosarcomas at the study institution. METHODS: This study reviews 46 cases of high grade surface osteosarcoma, comprised of 13 cases from the Mayo Clinic files and 33 from the authors' files. Histologic features were reviewed in all cases, and radiographs were reviewed in 29 cases. RESULTS: There was a definite male predominance, and 70% of the patients were in the second and third decades of life. Forty-four of the 46 patients had lesions involving the long bones, the most common site being the midportion of the femur. Radiographically, the majority of lesions showed dense to moderate mineralization with a fluffy, immature appearance. Radiating spicules of bone perpendicular to the long axis of the bone, characteristic of periosteal osteosarcoma, were sparse. Histologic findings were identical to those of conventional osteosarcoma. Overall, survival at 5 years was 46.1%. Statistical analysis revealed that marginal excision was associated with an increased risk of local recurrence and that the patients with Broders Grade 3 tumors had a better prognosis than those with Grade 4 tumors. A good response to chemotherapy was associated with better clinical outcome. CONCLUSIONS: High grade surface osteosarcoma is a rare subtype of surface osteoscarcoma that has a prognosis similar to that of conventional osteosarcoma, in contrast to the more common type of osteosarcoma arising on the surface of bone. Wide excision and effective systemic chemotherapy are associated with better clinical results.     

Second malignant neoplasms after treatment of childhood cancer

The aim of this study was to determine therapy-related risk factors for the development of second malignant neoplasm (SMN) after childhood cancer. The German Childhood Cancer Registry (GCCR) registers all childhood malignancies since 1980 including SMN. A nested case-control study with 238 SMN cases and 450 controls was conducted. A confirmatory, as well as an explorative, analysis was performed. Radiotherapy showed a small effect on the risk of SMN for doses >or=65 Gy. Regarding the chemotherapeutical agents, we saw increased Odds Ratios (OR) for high doses of cyclophosphamide (CP >8000 mg/m(2) OR=6.3 (95% Confidence Interval (CI): 1.3-30.2)), cisplatinum (DDP >435 mg/m(2) OR=2.8 (95% CI: 1.1-6.7)) and mercaptopurine (MP >5000 mg/m(2) OR=4.5 (95% CI: 1.1-18.9)). Patients jointly receiving high doses of MP (>5000 mg/m(2)) and dexamethasone (DEXA >or=1200 mg/m(2)) had an OR=6.9 (95% CI: 1.2-40.3). Our results could be added to those of other investigations to give indications for modifying future therapeutic strategies for childhood cancer.     

Cardiac damage after treatment of childhood cancer: A long-term follow-up

Background  

With improved childhood cancer cure rate, long term sequelae are becoming an important factor of quality of life. Signs of cardiovascular disease are frequently found in long term survivors of cancer. Cardiac damage may be related to irradiation and chemotherapy.     

Primary treatment of pelvic osteosarcoma. Report of five cases.

Five patients, ages 12 to 20 years, with nonresectable primary (Patients 2, 3, and 5) and metastatic (Patients 1 and 4) pelvic osteosarcomas were treated with intraarterial cisplatin and concurrent radiation therapy from 1983 to 1987. Long-term local tumor control was achieved in all five patients. Patients 1 and 3 are alive with no evidence of local recurrence or metastatic disease at 77 and 56 months of follow-up, respectively, since diagnosis of the pelvic tumor. Patients 2, 4, and 5 died of metastatic lung disease at 25, 39, and 12 months, respectively, after diagnosis of the pelvic tumor. Patient 4 had no clinical or radiologic evidence of local recurrence. Control of tumor growth in patients with pelvic osteosarcomas can be achieved with regional chemotherapy and concurrent radiation therapy. These patients also should receive adjuvant intensive systemic chemotherapy to increase the probability of eliminating potential subclinical metastatic disease.     

Outcome for adolescent and young adult patients with osteosarcoma: A report from the Children's Oncology Group

BACKGROUND:

There are conflicting data regarding age as a prognostic factor in osteosarcoma. The authors conducted a study evaluating the impact of age on prognosis in children and young adults with osteosarcoma enrolled on North American cooperative group trials.

METHODS:

Patients with high‐grade osteosarcoma of any site enrolled on North American cooperative group trials CCG‐7943, POG‐9754, INT‐0133, and AOST0121 were included in this study. Primary tumor site, age, sex, ethnicity, histologic response, and presence of metastatic disease at diagnosis were evaluated for their impact on overall survival (OS) and event‐free survival (EFS).

RESULTS:

A total of 1054 patients were eligible and had complete data available for the study. Age was not significantly associated with any other presenting covariate analyzed except sex. Age 18 or older was associated with a statistically significant poorer EFS (P = .019) and OS (P = .043). The 10‐year EFS and OS in patients <10, 10 to 17, and ≥18 years old were 55%, 55%, 37% and 68%, 60%, 41%, respectively. The poorer EFS in patients ≥18 years old was because of an increased rate of relapse. Presence of metastatic disease at diagnosis, poor histologic response, and pelvic tumor site were also associated with a poorer prognosis. In multivariate analysis, age continued to be associated with poorer EFS (P = .019) and OS (P = .049).

CONCLUSIONS:

In osteosarcoma, age 18 to 30 years is associated with a statistically significant poorer outcome because of an increased rate of relapse. Poorer outcome in adolescent and young adult patients is not explained by tumor location, histologic response, or metastatic disease at presentation. Cancer 2012. © 2012 American Cancer Society.