Determinants of peripheral blood count value in long‐term survivors of allogeneic hemopoietic stem cell transplantation

Hemopoeitic stem cell transplant (HSCT) recipients are monitored by regular complete blood picture (CBP). The reference ranges for acceptable values are undefined. We analysed the CBP in 228 stable HSCT survivors (median follow‐up 103 months, range 60–212) without transplant‐related medications and complications. Compared with donors, recipients had lower absolute neutrophil count (ANC) and platelet levels (Plt) and higher mean corpuscular volume (MCV), but comparable hemoglobin (Hb) and absolute lymphocyte count (ALC). There was significant donor–recipient correlation in all CBP parameters (Hb, ALC, ANC, MCV, Plt). Significant correlation was also found between levels of Hb, white cell and Plt among recipients. All counts were higher in patients with longer follow‐up. Donor and recipient gender, age and underlying diagnosis can influence stable CBP values. We conclude that both host and marrow factors influence CBP values in stably engrafted recipients. ‘Abnormal’ CBP values deviating from that in normal populations may not have clinical significance. Copyright © 2009 John Wiley & Sons, Ltd.     

Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long-term survival in a randomized study

Although surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer, long-term survival is not satisfactory and recurrence rate is high. We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival. We extended size and observation period of the study sample and performed a separate analysis for minimally resected patients. The trial was designed as a randomized, 2-armed study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure (defined as anatomical or minimal). Chemotherapy consisted of cisplatin (100 mg/m2 day 1) and etoposide (120 mg/m2 days 1-3) for 6 cycles. The primary endpoint was overall survival; secondary endpoint was disease-free survival (DFS). One hundred and forty patients entered the study: 70 were assigned to the adjuvant chemotherapy group and 70 to the control group. Groups were homogeneous for conventional risk factors. There was no clinically significant morbidity associated to chemotherapy. Patients were followed for a mean period of 40.31 +/- 30.86 months. A significant difference in overall (p = 0.02) and disease-free (p = 0.0001) survival was observed between patients undergoing adjuvant chemotherapy vs. control group. Adjuvant chemotherapy significantly improved both overall (p = 0.02) and DFS (p = 0.003) of anatomically resected patients, but only the DFS (p = 0.02) of minimally resected patients. Our results confirm that adjuvant chemotherapy may have a real impact on long-term survival in patients with stage IB nonsmall cell lung cancer being this effect especially evident for those anatomically resected.     

Cancer survivors' experiences of discharge from hospital follow-up

Discharge from hospital follow-up is a key time point in the cancer journey. With recommendations for earlier discharge of cancer survivors, attention to the discharge process is likely to become increasingly important. This study explored cancer survivors' experiences of discharge from hospital follow-up. Survivors of breast, colorectal and prostate cancer (n= 1275), 5-16 years post diagnosis were approached to take part in a questionnaire survey. The questionnaire included questions about discharge status, provision of time/information prior to discharge, feelings at discharge and satisfaction with how discharge was managed. Completed questionnaires were returned by 659 survivors (51.7%). Approximately one-third of respondents were not discharged from follow-up 5-16 years post diagnosis. Of those discharged, a substantial minority reported insufficient time (27.9%), information (24.5-45.0%) or adverse emotions (30.9%) at the time of discharge. However, 90.6% of respondents reported satisfaction with how discharge from hospital follow-up was managed. Despite high levels of satisfaction, discharge of cancer survivors from hospital follow-up could be improved with the provision of additional time, information and support. Better structuring of the final hospital appointment or a review appointment in primary care at this time could help to ensure that discharge from hospital follow-up is managed optimally for cancer survivors.     

Long‐term results (>25 years) of a randomized,prospective clinical trial evaluating chemotherapy in patients with high‐grade,operable osteosarcoma

BACKGROUND:

The authors present the long‐term follow‐up (>25 years) data from 1 of the original prospective, randomized trials that compared adjuvant chemotherapy with expectant management in patients with high‐grade, localized osteosarcoma. In addition, the value of pathologic necrosis induced by a single cycle of neoadjuvant chemotherapy was analyzed as a predictive marker of disease‐free and overall survival.

METHODS:

Fifty‐nine patients with high‐grade, localized osteosarcoma were enrolled in a prospective trial that was performed between 1981 and 1984 at the University of California‐Los Angeles (UCLA). Patients were randomized to receive either adjuvant chemotherapy or observation after surgical resection. Long‐term outcomes, follow‐up, and pathologic review of all available histologic sections were performed.

RESULTS:

The 25‐year disease‐free survival rate was 28% for patients who received adjuvant chemotherapy compared with 15% for the untreated patients (P = .02). The overall survival rate at 25 years was also significantly higher for treated patients versus untreated patients (38% vs 15%; P = .02). Tumor necrosis >90% after a single round of chemotherapy was a statistically significant predictor of overall survival and disease‐free survival for patients who received adjuvant therapy (164 months vs 65 months [P = .04] and 141 months vs 14 months [P < .01], respectively).

CONCLUSIONS:

Patients with high‐grade, localized osteosarcoma who received adjuvant chemotherapy after undergoing definitive surgical resection had a statistically significant benefit in disease‐free and overall survival that was maintained through 25 years. Tumor necrosis after just 1 cycle of neoadjuvant chemotherapy and radiation was predictive of overall survival and disease‐free survival in patients who received adjuvant chemotherapy. Cancer 2012. © 2012 American Cancer Society.     

Secondary malignancies in pediatric cancer survivors: Perspectives and review of the literature

With continuing improvements in the successful treatment of pediatric malignancies, long term survivors of pediatric cancers and their providers are faced with new oncologic issues regarding long‐term morbidities. As pediatric cancer survivors have matured into adulthood, the development of secondary malignancies has become a significant issue for these patients. Whether a consequence of treatment for the patient's original cancer, such as chemotherapy, ionizing radiation, or hematopoietic stem cell transplantation, secondary malignancies now present patients and providers with new challenges regarding treatment, surveillance and counseling. We review the major risk factors for secondary malignancies in pediatric cancer survivors, with particular emphasis on important molecular and cytogenetic risk factors, both inherited and acquired. We conclude with a discussion of recommendations for surveillance and counseling of these patients.     

Predictions of survival up to 10 years after diagnosis for European women with breast cancer in 2000–2002

Few studies have addressed longer‐term survival for breast cancer in European women. We have made predictions of 10‐year survival for European women diagnosed with breast cancer in 2000–2002. Data for 114,312 adult women (15–99 years) diagnosed with a first primary malignant cancer of the breast during 2000–2002 were collected in the EUROCARE‐4 study from 24 population‐based cancer registries in 14 European countries. We estimated relative survival at 1, 5, and 10 years after diagnosis for women who were alive at some point during 2000–2002, using the period approach. We also estimated 10‐year survival conditional on survival to 1 and 5 years after diagnosis. Ten‐year survival exceeded 70% in most regions, but was only 54% in Eastern Europe, with the highest value in Northern Europe (about 75%). Ten‐year survival conditional on survival for 1 year was 2–6% higher than 10‐year survival in all European regions, and geographic differences were smaller. Ten‐year survival for women who survived at least 5 years was 88% overall, with the lowest figure in Eastern Europe (79%) and the highest in the UK (91%). Women aged 50–69 years had higher overall survival than older and younger women (79%). Six cancer registries had adequate information on stage at diagnosis; in these jurisdictions, 10‐year survival was 89% for local, 62% for regional and 10% for metastatic disease. Data on stage are not collected routinely or consistently, yet these data are essential for meaningful comparison of population‐based survival, which provides vital information for improving breast cancer control.     

Long‐term follow‐up of patients with resected pancreatic cancer following vaccination against mutant K‐ras

K‐ras mutations are frequently found in adenocarcinomas of the pancreas and can elicit mutation‐specific immune responses. Targeting the immune system against mutant Ras may thus influence the clinical course of the disease. Twenty‐three patients who were vaccinated after surgical resection for pancreatic adenocarcinoma (22 pancreaticoduodenectomies, one distal resection), in two previous Phase I/II clinical trials, were followed for more than 10 years with respect to long‐term immunological T‐cell reactivity and survival. The vaccine was composed of long synthetic mutant ras peptides designed mainly to elicit T‐helper responses. Seventeen of 20 evaluable patients (85%) responded immunologically to the vaccine. Median survival for all patients was 27.5 months and 28 months for immune responders. The 5‐year survival was 22% and 29%, respectively. Strikingly, 10‐year survival was 20% (four patients out of 20 evaluable) versus zero (0/87) in a cohort of nonvaccinated patient treated in the same period. Three patients mounted a memory response up to 9 years after vaccination. The present observation of long‐term immune response together with 10‐year survival following surgical resection indicates that K‐ras vaccination may consolidate the effect of surgery and represent an adjuvant treatment option for the future.     

Gastric stump cancer after distal gastrectomy for benign gastric ulcer in a population-based study

The risk of cancer in the gastric remnant after distal gastrectomy for benign ulcer disease has been assessed mainly in studies of small sample size, selected series and limited follow-up time. This was a population-based cohort study of patients who had undergone distal gastrectomy for benign ulcer disease in 1964-2008 in Sweden. Data for follow-up for cancer and censoring for death were obtained from nationwide registries of Cancer and Population, respectively. The number of observed cancer cases in the gastrectomy cohort was divided by the expected number, calculated from the cancer incidence of the Swedish population of corresponding age, sex and calendar year. Relative risks were presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). The distal gastrectomy cohort included 18,912 patients and 323,676 person-years at risk. The observed total number of gastric stump cancers (n = 140) was not higher than expected (SIR 0.84, 95% CI 0.71-0.99). There was no increased SIR with latency periods shorter than 30 years; increase was seen only among patients who had undergone gastric resection over 30 years earlier (SIR 2.29, 95% CI 1.38-3.57). Sex, age, ulcer location and type of surgical reconstruction were not associated with any considerable differences in SIR. In conclusion, this large population-based study revealed an increased risk of cancer in the gastric remnant only 30 years or longer after gastric resection for benign disease, whereas other factors did not influence this risk.     

Prognostic factors and long‐term outcomes of childhood nasopharyngeal carcinoma

BACKGROUND:

The authors studied the survival and long‐term morbidities of children with nasopharyngeal carcinoma (NPC).

METHODS:

This was a retrospective review of children with NPC who were treated at St. Jude Children's Research Hospital between 1961 and 2004. Prognostic factors and long term effects of therapy were analyzed.

RESULTS:

Fifty‐nine patients (median age, 14.1 years) were identified. Most were male (66.1%) and black (54.2%) and had lymphoepithelioma (93.2%). Thirty‐five patients had stage IV disease (59.3%), 20 patients had stage III disease (33.9%), and 4 patients had stage II disease (6.8%). All patients received radiotherapy (RT) to the primary tumor, and most received cervical RT (98.3%) and chemotherapy (88.1%). The 15‐year survival and event‐free survival (EFS) rates were 67.2% ± 7.5% and 63.5% ± 7.8%, respectively. Five patients (8.5%) developed subsequent malignancies 8.6 to 27 years after NPC diagnosis. EFS was improved in patients who were diagnosed after 1980 (74.8% ± 10% vs 45.5% ± 10.1%; P = .031), in patients who had stage III disease compared with patients who had stage IV disease (79.3% ± 9.6% vs 56.2% ± 11.8%; P = .049), in patients who received cisplatin (81% ± 10.7% vs 45.8% ± 9.7%; P = .013), and in patients who received ≥50 grays of RT (71.4% ± 9.3% vs 43.8% ± 11.6%; P = .048). White patients had higher distant failure rates than black patients (41.7% ± 10.4% vs 15.6 ± 6.5%; P = .045). The 15‐year cumulative incidence (CI) of any morbidity was 83.7% ± 5.4%, the CI of sensorineural hearing loss was 52.9% ± 6.7%, the CI of primary hypothyroidism was 42.7% ± 6.6%, and the CI of growth hormone deficiency (GHD) was 14.1% ± 4.7%. Dose‐response relations were observed between the RT dose and primary hypothyroidism and GHD.

CONCLUSIONS:

The outcome of children with NPC improved over the past 4 decades with the use of cisplatin‐based chemotherapy and higher RT doses. However, many survivors had long‐term treatment‐related morbidities. Cancer 2011. © 2010 American Cancer Society.     

Long‐term cancer survivors experience work changes after diagnosis: results of a population‐based study

Background: Although cancer survivorship is increasing with improved diagnosis and treatments, few studies have explored employment changes and the factors related to this change among cancer survivors. Therefore, we aim to explore the prevalence of employment problems in long‐term cancer survivors. In addition, we explored what patient or tumour characteristics predicted employment changes. Methods: All 1893 long‐term survivors of prostate cancer, endometrial cancer, non‐Hodgkin's lymphoma, and Hodgkin's lymphoma diagnosed between 1989 and 1998 in the area of the Comprehensive Cancer Centre South, The Netherlands were included in a population‐based cross‐sectional survey. Results: Response rate was 80% (n=1511). After excluding survivors without a job before diagnosis, 403 survivors remained; 197 (49%) experienced no changes in their work situation following cancer diagnosis, 69 (17%) were working fewer hours, and 137 (34%) stopped working or retired. A medium educational level was significant in reducing the risk of work changes. Being older, having more than one comorbid condition, being treated with chemotherapy, and disease progression were significant independent predictors of work changes after cancer. Experiencing work changes was associated with lower physical functioning but positively associated with social well‐being. Discussion: Long‐term cancer survivors experience work changes after diagnosis and treatment, and clinical factors significantly predicted work change after cancer. As such, our study underscores the importance of rehabilitation programs in improving the return to work after cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

Appraisal of the cancer experience by family members and survivors in long-term survivorship

This study assessed the appraisal of the stressfulness of the cancer experience and its correlates for family members and older survivors living in the long-term survivorship phase of the disease. On average, family members appraised the cancer experience as more stressful than their surviving relatives. Beliefs about the effect of the diagnosis and treatment on family members were important correlates for both family members and survivors in the appraisal process. Cancer characteristics were not related to appraisal for survivors, but stage at diagnosis was associated with a more stressful appraisal for family members. Demographic characteristics were unrelated to appraisal for family members, but being African-American was linked to a less stressful appraisal for survivors. These findings highlight the stressful impact of the cancer experience on family members and can help guide health care interventions which include family members from African-American and White ethnicities.     

Cancer risks after solid organ transplantation and after long‐term dialysis

Immunosuppression involves an inability to control virus infections and increased incidence of virus‐associated cancers. Some cancers without known viral etiology are also increased, but data on exactly which cancer forms are increased has been inconsistent. To provide a reliable and generalizable estimate, with high statistical power and long follow‐up time, we assessed cancer risks using comprehensive, population‐based registries in two different countries and from two different immunosuppressed patient groups (solid organ transplant recipients (OTRs) and long‐term dialysis patients (LDPs)). National registries in Denmark and Sweden identified 20,804 OTRs and 31,140 LDPs that were followed up using national cancer registries. Standardized incidence ratios (SIR) compared to the general population were estimated. We found highly similar results, both for the two different countries and for the two different immunosuppressed cohorts, namely an increased incidence for the following specific cancer forms: Non‐melanoma skin cancer (NMSC), non‐Hodgkin's lymphoma and cancers of the lip, kidney, larynx and thyroid. The SIR for overall cancer among OTRs was 3.5 [n = 2,142, 95% CI, 3.4–3.7] in Sweden, 2.9 [n = 1,110, 95% CI, 2.8–3.1] in Denmark and 1.6 [n = 1,713, 95% CI, 1.5–1.6] among LDP. The SIR for NMSC among OTRs was 44.7 [n = 994, 95% CI, 42–47.5] in Sweden and 41.5 [n = 445, 95% CI, 37.8–45.5] in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n = 304, 95% CI, 4.7–5.9]). In summary, an increased SIR for a specific, similar set of cancer forms is consistently found among the immunosuppressed. Conceivable explanations include surveillance bias and immunosuppression‐related susceptibility to viral infections.     

Long‐term adverse effects after retropubic and robot‐assisted radical prostatectomy. Nationwide,population‐based study

Background and Objectives

Surgery for prostate cancer is associated with adverse effects. We studied long‐term risk of adverse effects after retropubic (RRP) and robot‐assisted radical prostatectomy (RARP).

Methods

In the National Prostate Cancer Register of Sweden, men who had undergone radical prostatectomy (RP) between 2004 and 2014 were identified. Diagnoses and procedures indicating adverse postoperative effects were retrieved from the National Patient Register. Relative risk (RR) of adverse effects after RARP versus RRP was calculated in multivariable analyses adjusting for year of surgery, hospital surgical volume, T stage, Gleason grade, PSA level at diagnosis, patient age, comorbidity, and educational level.

Results

A total of 11 212 men underwent RRP and 8500 RARP. Risk of anastomotic stricture was lower after RARP than RRP, RR for diagnoses 0.51 (95%CI = 0.42‐0.63) and RR for procedures 0.46 (95%CI = 0.38‐0.55). Risk of inguinal hernia was similar after RARP and RRP but risk of incisional hernia was higher after RARP, RR for diagnoses 1.48 (95%CI = 1.01‐2.16), and RR for procedures 1.52 (95%CI = 1.02‐2.26).

Conclusions

The postoperative risk profile for RARP and RRP was quite similar. However, risk of anastomotic stricture was lower and risk of incisional hernia higher after RARP.     

Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma

The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case–control and cohort studies. In the case–control study, 397 HCC cases from medical centers were compared with 410 community‐based non‐HCC controls. All of them were anti‐HCV‐seropositive, HBsAg‐seronegative with serum HCV RNA levels ≥1,000 IU/mL. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti‐HCV‐seropositive individuals were followed from 1991 to 2008 to assess the long‐term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow‐up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64 vs. 55%, p < 0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0 × 10⁶ IU/mL) than those infected with HCV non‐1b (1.2 × 10⁶ IU/mL, p < 0.001). The multivariate‐adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non‐1b was 1.43 (1.02–2.02). After the long‐term follow‐up, the cumulative lifetime (30–80 years old) HCC risk was 19.2 and 29.7% for patients infected with HCV non‐1b and 1b, respectively (p < 0.001). The multivariate‐adjusted hazard ratio (95% CI) was 1.85 (1.06–3.22) for HCV 1b compared to non‐1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b.     

Long‐term follow‐up of the risk for cervical intraepithelial neoplasia grade 2 or worse in HPV‐negative women after conization

Little research has been conducted on the long‐term value of human papillomavirus (HPV) testing after conization. We investigated whether cytology adds to the value of a negative HPV test for long‐term prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In addition, we compared risk of CIN2+ following a negative HPV test in women after conization with that in women from the general population. During 2002–2005, 667 women treated for CIN2+ were tested for HPV and cytology 46 months after conization. Only HPV‐negative women were included. Women participating in routine screening were age‐matched with post‐conization HPV‐negative women, leaving 13,230 and 477 women, respectively, for analysis. By linkage to the Pathology Data Bank, we identified all cases of CIN2+ by December 2013. The 3‐, 5‐, 8‐ and 10‐year risks for CIN2+ were 0.7, 0.9, 2.8 and 5.7% after a negative HPV test and 0.5, 0.8, 2.9 and 6.1% in HPV and cytology‐negative women. HPV‐negative women in the general population had similar 3‐year and 5‐year risks of 0.4 and 1.0%; thereafter, they had lower risks of 1.9% at 8 years and 2.7% at 10 years. Our results indicate that HPV testing may be used as a test of cure after conization. In the first 5 years after testing, the risk for CIN2+ of women who were HPV‐negative at 34 months after conization was similar to that of HPV‐negative women in the general population. After 67 years, however, women who have undergone conization may be at higher risk for CIN2+.     

Prospective assessment of quality of life in long‐term ovarian cancer survivors

The objective of our study was to compare prospectively the QoL in long‐term ovarian cancer survivors with short‐term survivors and to explore discriminating variables between short‐term and long‐term survival. Thirty‐three patients were included, 22 died within 5 years post diagnosis and 11 survived beyond 10 years. QoL data were collected pre‐treatment (baseline), 1‐year post diagnoses and for long‐term survivors 10 years post‐treatment using the EORTC QLQ‐C30. At baseline, there was no difference in terms of FIGO stage, residual tumor and adjuvant chemotherapy. Significantly, more short‐term survivors (96%) had intra operative ascites as compared to long‐term survivors (55%) (p=0.01). Before treatment, short‐term survivors had clinically significantly lower QoL scores on the physical functioning (mean 75.45) and role functioning scale (mean 68.94) compared to long‐term survivors (mean 68.94 and 84.85, respectively). They also reported higher levels of symptoms. One year post‐diagnosis, QoL scores were comparable in most domains. Long‐term survivors had a significantly better global QoL but more insomnia. Emotional functioning and global QoL/health status improved significantly from baseline to 1‐year post‐diagnosis and remained relatively stable at the 10‐year follow‐up. The presence of intra operative ascites and a supporting social network were identified as significant variables that discriminated between short‐term and long‐term survival. Compared to a reference sample, long‐term survivors showed similar QoL scores but more dyspnoea. Although ovarian cancer patients do not belong to the most prevalent survivor populations, we found that long‐term survivors have QoL scores similar to females without a history of cancer.