Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study

Background

Contemporary risk-directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome.

Methods

The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation.

Results

The overall 5-year event-free survival was 84.4% (95% confidence interval [CI], 80.6–88.3) and 5-year overall survival 88.9% (95% CI, 85.5–92.4). Independent factors associated with lower 5-year event-free survival were male sex (80.4%, [95% CI, 74.8–86.4] vs. 88.9%, [95% CI, 84.1–93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2–87.4] vs. 87.1%, [95% CI, 83.4–90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5-year event-free survival (33.3% [95% CI, 11.6–96.1] vs. 83.0% [95% CI, 77.5–88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2–14.5], p < .001).

Conclusions

These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL.     

Disparities in prostate cancer screening,diagnoses, management,and outcomes between Indigenous and non-Indigenous men in a universal health care system

Background

Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought.

Methods

An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals.

Results

Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50–70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25–65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2–4.2; p < .01) than non-Indigenous men.

Conclusions

Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.     

Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia

BACKGROUND:

A study was undertaken to analyze the survival of chronic lymphocytic leukemia (CLL) patients relative to age‐matched individuals in the general population and determine the age‐stratified utility of prognostic testing.

METHODS:

All 2487 patients diagnosed with CLL between January 1995 and June 2008 and cared for in the Mayo Clinic Division of Hematology were categorized by age at diagnosis and evaluated for differences in clinical characteristics, time to first treatment, and overall survival (OS).

RESULTS:

Among Rai stage 0 patients, survival was shorter than the age‐matched general population for patients aged <55 years (P < .001), 55 to 64 years (P < .001), and 65 to 74 years (P < .001), but not those aged ≥75 years at diagnosis (P = not significant). CD38, IGHV mutation, and ZAP‐70 each predicted time to first treatment independent of stage for all age groups (all P < .04), but had less value for predicting OS, particularly as age increased. IGHV and fluorescent in situ hybridization (FISH) predicted OS independent of stage for patients aged <55 years (P ≤ .001), 55 to 64 years (P ≤ .004), and 65 to 74 years (P ≤ .001), but not those aged ≥75 years. CD38 and ZAP‐70 each predicted OS independent of stage for only 2 of 4 age categories. Among Rai 0 patients aged <75 years, survival was shorter than the age‐matched population only for IGHV unmutated (P < .001) patients or those with unfavorable FISH (P < .001).

CONCLUSIONS:

Survival of CLL patients aged <75 years is shorter than the age‐matched general population regardless of disease stage. Among patients aged <75 years, the simple combinations of stage and IGHV or stage and FISH identifies those with excess risk of death relative to the age‐matched population. Although useful for predicting time to first treatment independent of stage for patients of all ages, prognostic testing had little utility for predicting OS independent of stage among patients aged ≥75 years. Cancer 2010. © 2010 American Cancer Society.     

Treatment patterns of aging Americans with differentiated thyroid cancer

BACKGROUND:

The incidence of differentiated thyroid cancer (DTC) increases with age. Total thyroidectomy, often followed by radioactive iodine (RAI), is recommended for patients who have tumors that measure ≥1 cm in greatest dimension. In the current study, the authors assessed the use of thyroidectomy and RAI among elderly patients with DTC and the effects on survival.

METHODS:

Adults aged ≥45 years with DTC ≥1 cm in the Surveillance, Epidemiology, and End Results database from 1988 to 2003 were included. Bivariate and multivariate analyses were used to measure associations between demographic, clinical, and pathologic characteristics and the likelihood of receiving treatment according to current practice guidelines.

RESULTS:

Of 8899 patients who were identified, 26% were ages 65 years to 79 years, and 5% were aged ≥80 years. Compared with younger patients, patients aged ≥ 65 years were more likely to have larger tumors, stage IV disease, extrathyroid extension, and nonpapillary histology. Elderly patients were less likely to undergo total thyroidectomy (74% vs 80%; P < .001) or to receive RAI (47% vs 54%; P < .001). These trends were most pronounced among those aged ≥80 years. Among the patients who did not undergo surgery, elderly patients did not report higher rates of contraindications to surgery. In multivariate analysis, the groups ages 65 years to 79 years and aged ≥80 years were associated with lower rates of total thyroidectomy (odds ratio, 0.77 and 0.43, respectively; P < .001) and RAI (odds ratio, 0.85 [P < .01] and 0.39 [P < .001], respectively). Among elderly patients, predictors of worse survival included no surgery (hazard ratio, 5.51; P < .001) and no RAI (hazard ratio, 1.36; P < .001).

CONCLUSIONS:

Elderly patients with DTC received less aggressive surgical and RAI treatment than younger patients despite having more advanced disease and the improved survival associated with these treatments among elderly patients. Long‐term outcomes should be measured to determine the impact of this apparent discrepancy in care. Cancer 2010. © 2010 American Cancer Society.     

Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation

BACKGROUND:

A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features.

METHODS:

The authors searched for patients who had AML with cuplike nuclei at their institution over a 10‐year interval. A strict definition for cuplike nuclei was used: ≥10% blasts with nuclear invaginations in ≥25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei.

RESULTS:

In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French‐American‐British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms‐like tyrosine kinase 3 (FLT3)‐internal tandem duplication (ITD) (86% vs 38%, respectively; P = .002); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001); both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P = .003); bone marrow blast count (90% vs 84%; P = .016); myeloperoxidase positivity (95% vs 30% blasts; P = .001); higher D‐dimer levels (>5000 ng/mL vs 569 ng/mL; P = .001); and the absence of CD7 (91% vs 52%; P = .007), CD34 (82% vs 5%; P < .0001), and human leukocyte antigen, D‐related (59% vs 10%; P = .001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3‐ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively.

CONCLUSIONS:

Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3‐ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms. Cancer 2009. © 2009 American Cancer Society.     

Psychosocial outcomes in long-term Dutch adult survivors of childhood cancer: The DCCSS-LATER 2 psycho-oncology study

Background

This study compares a comprehensive range of psychosocial outcomes of adult childhood cancer survivors (CCS) to general population-based references and identifies sociodemographic and medical risk factors.

Methods

CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963–2001) part 2 (attained age ≥18 years, diagnosed <18 years, ≥5 years since diagnosis) completed the Rosenberg Self-Esteem Scale, Hospital Anxiety and Depression Scale, Distress Thermometer, Self-Rating Scale for Post-Traumatic Stress Disorder, and the Short Form-36 (Health Related Quality of Life). CCS’ scores were compared with references using analysis of variances and logistic regression analysis, controlling for age and sex (p < .05). Risk factors for worse psychosocial outcomes were assessed with regression analyses (p < .05).

Results

CCS, N = 1797, mean age 35.4 years, 49.0% female, all ≥15 years since diagnosis, participated. Three percent reported posttraumatic stress disorder because of childhood cancer and 36.6% experienced clinical distress. CCS did not differ from references on self-esteem and anxiety but were less depressed (d = −.25), and scored poorer on all health-related quality of life scales, except for bodily pain (.01 ≤ d  ≥  −.36). Female sex, lower educational attainment, not being in a relationship, and being unemployed were negatively associated with almost all psychosocial outcomes. Except for a central nervous system tumor diagnosis, few medical characteristics were associated with psychosocial outcomes.

Conclusion

CCS appear resilient regarding mental health but have slightly poorer health-related quality of life than references. Sociodemographic characteristics and central nervous system tumors were related to most psychosocial outcomes, but no clear pattern was observed for other medical factors. Future studies should address additional factors in explaining CCS’ psychosocial functioning, such as coping, social support, and physical late effects.     

Implementation and evaluation of a remote geriatric assessment and intervention program in Brazil

Background

This study sought to determine the feasibility and acceptability of a remote geriatric assessment (GA) and implementation (GAIN) program in Brazil. The authors also explored the effect of this program on health-related quality of life (HR-QOL) outcomes 3 months after initiating treatment.

Methods

This is a longitudinal study enrolling older adults (65+ years), diagnosed with any type of solid tumor, scheduled to initiate chemotherapy in a networked Brazilian cancer center. The GA was performed through telehealth. We assessed the feasibility of the remote GA, acceptability to patients, and changes in patient-centered outcomes (HR-QOL, mood, function) from baseline to month 3. Linear mixed model analysis was done, adjusting for age, gender, race, income, and disease stage.

Results

Fifty-six patients completed all intended assessments. Notably, the threshold of feasibility was 70% and there was 92% complete adherence. Average age was 76 years old (SD = 7.2). Most patients were female (57%), married (59%), and had a college degree (46%). The most common diagnoses were gastrointestinal (39%) and gynecological cancers (18%); most were diagnosed at an advance disease stage (77%). A total of 32 patients were referred to a remote appointment and 86% followed this recommendation(s). Significant improvement in Functional Assessment of Cancer Therapy - General FACT-G (mean difference, 6.04; p < .001), Geriatric Depression Scale (mean difference, −0.86; p = .008), and instrumental activities of daily living ratio (mean difference, 0.17; p < .001) were found.

Conclusion

Remote GAIN is feasible and acceptable to older adults with cancer receiving treatment in Brazil. The authors also found significant improvement in HR-QOL outcomes over time. Notably, this GAIN program could guide early detection of chemotherapy toxicity and improving patient-reported outcomes in low-resource environments.     

Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols

Background

Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread.

Methods

A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998– 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival.

Results

Median overall survival (mOS) improved over time (6.7 months in 1998–2007 to 11.8 months in 2008–2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2–2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4–3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02–2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1–3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4–4.0]), DFI >6 months (OR, 2.4 [1.5–4.0]), and body mass index ≥30 (OR, 2.3 [1.1–4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24–0.55).

Conclusion

These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials.

Plain Language Summary

• After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body.
• This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns.
• Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients.
• These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

     

Sex‐specific attention problems in long‐term survivors of pediatric acute lymphoblastic leukemia

BACKGROUND:

Neurocognitive problems are a frequent outcome of chemotherapy for pediatric leukemia, although individual differences exist in patient outcome. Sex of the patient and age at diagnosis are 2 characteristics that have been associated with differential outcomes. The relation between these patient characteristics and specific attention deficits (ie, initiating, inhibiting, shifting, focusing, sustaining attention, and working memory) has not been well researched. The purpose of this study was to evaluate the pattern of attention problems in male and female long‐term survivors of pediatric acute lymphoblastic leukemia (ALL).

METHODS:

One hundred three long‐term survivors (ie, ≥5 years from diagnosis; 51% boys, mean age at diagnosis of 3.9 years, and mean time since diagnosis 7.5 years) completed standardized measures of basic and complex attention skills related to anterior (ie, inhibition, shifting attention, working memory), posterior (ie, focusing), and subcortical brain systems (ie, sustaining).

RESULTS:

Treatment intensity was related to sustained attention, with those patients treated on high‐risk protocols displaying significantly lower performance. Girls performed worse than boys on measures related to the anterior attention system (ie, shifting attention, P < .042) and the subcortical attention system (ie, sustained attention, P < .001), whereas boys performed worse than girls on different measures of anterior control (ie, inhibition, P < .039; working memory, P < .003).

CONCLUSIONS:

The results of this study suggest that children diagnosed with and treated for pediatric ALL perform poorly on select measures of attention and executive control, and that this performance is influenced by sex and treatment intensity. Cancer 2009. © 2009 American Cancer Society.     

Effect of body mass index on the outcome of children with acute myeloid leukemia

BACKGROUND:

The effect of body mass index (BMI) on the treatment outcomes of children with acute myeloid leukemia (AML) is unclear and needs further evaluation.

METHODS:

Children with AML (n = 314) who were enrolled in 4 consecutive St. Jude protocols were grouped according to BMI (underweight, <5th percentile; healthy weight, 5th to 85th percentile; and overweight/obese, ≥85th percentile).

RESULTS:

Twenty‐five patients (8%) were underweight, 86 patients (27.4%) were overweight/obese, and 203 patients (64.6%) had healthy weight. The 5‐year overall survival rate of overweight/obese patients (46.5% ± 7.3%) was lower than the rate of patients with healthy weight (67.1% ± 4.3%; P < .001); underweight patients also tended to have lower survival rates (50.6% ± 10.7%; P = .18). In a multivariable analysis that was adjusted for age, leukocyte count, French‐American‐British classification, and study protocols, patients with healthy weight had the best survival rate among the 3 groups (P = .01). When BMI was considered as continuous variable, patients with lower or higher BMI percentiles had worse survival (P = .03). There was no difference in the occurrence of induction failure or relapse among BMI groups, although underweight and overweight/obese patients had a significantly higher cumulative incidence of treatment‐related mortality, especially because of infection (P = .009).

CONCLUSIONS:

An unhealthy BMI was associated with worse survival and more treatment‐related mortality in children with AML. Meticulous supportive care with nutritional support and education, infection prophylaxis, and detailed laboratory and physical examination is required for these patients. These measures, together with pharmacokinetics‐guided chemotherapy dosing, may improve outcome. Cancer 2012. © 2012 American Cancer Society.     

Infections and association with different intensity of chemotherapy in children with acute myeloid leukemia

BACKGROUND:

The objectives were to compare infections during different intensities of therapy in children with acute myeloid leukemia (AML).

METHODS:

Subjects were children enrolled in Children's Cancer Group 2891 with AML. In phase 1 (induction), patients were randomized to intensive or standard timing. In phase 2 (consolidation), those with a family donor were allocated allogeneic stem cell transplantation (SCT); the remainder were randomized to autologous SCT or chemotherapy. This report compares infections between different treatments on an intent‐to‐treat basis.

RESULTS:

During phase 1, intensive timing was associated with more bacterial (57.7% vs 39.4%; P < .001), fungal (27.4% vs 9.9%; P < .001), and viral (14.0% vs 3.9%; P < .001) infections compared with standard timing. During phase 2, chemotherapy was associated with more bacterial (56.5% vs 40.1%; P = .005), but similar fungal (9.5% vs 6.1%; P = 1.000) and viral (4.2% vs 12.9%; P = .728) infections compared with allogeneic SCT. No differences between chemotherapy and autologous SCT infections were seen. Fatal infections were more common during intensive compared with standard timing induction (5.5% vs 0.9%; P = .004). Infectious deaths were similar between chemotherapy, autologous SCT, and allogeneic SCT.

CONCLUSIONS:

Prevalence of infection varies depending on the intensity and type of treatment. This information sheds insight into the mechanisms behind susceptibility and outcome of infections in pediatric AML. Cancer 2009. © 2009 American Cancer Society.     

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study

Background

Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes.

Methods

Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve.

Results

Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001–.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001–.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001–.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors.

Conclusion

Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.     

Blinatumomab or Inotuzumab Ozogamicin as Bridge to Allogeneic Stem Cell Transplantation for Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis

BackgroundBlinatumomab and inotuzumab ozogamicin are now widely used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).Patients and MethodsWe have reported the clinical course of 34 adult patients with r/r B-ALL receiving blinatumomab or inotuzumab ozogamicin at our institution from 2009 to 2019.ResultsBlinatumomab-based salvage therapy was applied for overt r/r B-ALL (n = 13) or minimal residual disease (MRD) positivity (n = 5). Of the 13 patients with r/r B-ALL, 9 (69%; 95% confidence interval [CI], 39%-91%) achieved complete remission (CR), with 78% of CR patients (95% CI, 40%-97%) reaching MRD negativity. MRD negativity was also achieved in all 5 patients treated for MRD positivity. The 1-year overall survival of patients receiving blinatumomab for r/r B-ALL and MRD positivity was 54% (n = 13; 95% CI, 26%-81%) and 80% (n = 5; 95% CI, 44-100), respectively. In the inotuzumab ozogamicin group, all 16 patients were treated for overt r/r B-ALL. The rate of CR was 94% (95% CI, 70%-100%), with 67% (95% CI, 38%-88%) of CR patients reaching MRD negativity. The 1-year OS after the first application of inotuzumab ozogamicin was 46% (95% CI, 18%-74%). Of those patients receiving blinatumomab and inotuzumab ozogamicin as a bridge-to-transplant strategy, 79% and 80%, respectively, proceeded to allogeneic stem cell transplantation. The most frequent drug-specific adverse events were similar to those previously reported, including cytokine release syndrome, capillary leak syndrome, and neurotoxicity for blinatumomab and transplant-associated veno-occlusive disease of the liver for inotuzumab ozogamicin.ConclusionTogether with previous observations from phase III clinical trials, these data suggest that blinatumomab and inotuzumab ozogamicin are highly effective salvage regimens in r/r B-ALL.     

Discordance between clinical and pathologic staging and the timeliness of care of non-small cell lung cancer patients diagnosed with operable tumors

Aim

This study was performed to evaluate concordance between clinical and pathologic staging of non-small cell lung cancer (NSCLC) in our hospital network.

Methods

We retrospectively reviewed records of 417 patients with NSCLC who received curative surgery and whose pathology was evaluated in our hospital between 2016 and 2021. Cytology, tissue pathology, and associated clinical, surgical, and imaging information were retrieved from hospital digital records.

Results

The cohort included 214 female and 203 male patients aged 20.6–85.8 years. Median times among staging computed tomography and surgery (105 days [interquartile range (IQR) 77.0–143.0]), positron emission tomography and surgery (78.5 days [IQR 56.0–109.0]), and endobronchial ultrasound-guided transbronchial needle aspiration and surgery (59 days [IQR 42–94]) indicated that Australian guidelines of <42 days between original referral and commencement of treatment were not being met in the majority of cases. Discordance between clinical TNM (cTNM) and pathologic TNM staging was 25.9%, including 18.4% cases that were clinically understaged and two patients with undetected stage IVA disease. cTNM understaging was significantly associated with time between the final staging investigation and surgery (p = .023), pleural (p < .05) and vessel (p < .05) invasion, and diagnosis of high-grade adenocarcinoma (p = .001).

Conclusion

Discordance between clinical and pathologic staging of NSCLC is associated with tumor histopathologic characteristics and treatment delays. Although tumor factors that lead to discordant staging cannot be controlled, reduced time to surgery may have resulted in better outcomes for some patients in this potentially curable lung cancer cohort.     

Defining the course and prognosis of adults with acute lymphocytic leukemia in first salvage after induction failure or short first remission duration

BACKGROUND:

Results from salvage therapy in adult patients with acute lymphocytic leukemia (ALL) are wide‐ranging and depend on several disease and patient characteristics. The objectives of this study were to define the prognosis for adult patients with ALL after first salvage through multivariate analyses of patient and disease characteristics.

METHODS:

Adults with ALL who had primary resistance to frontline therapy or who had a disease recurrence after a first complete response (CR) duration <1 year were analyzed. Multivariate analyses for subsequent CR and survival were conducted.

RESULTS:

Seventy‐five of 245 patients (31%) achieved CR. The median CR duration was 5 months, the median survival was 4.7 months. In multivariate analysis, independent poor prognostic factors for not achieving CR were age >55 years, bone marrow blasts ≥20%, and platelet count <75 × 10⁹/L. Variables that were associated independently with shorter survival were age >55 years, bone marrow blasts ≥20%, platelet count <75 × 10⁹/L, albumin level <3 g/L, and lactic dehydrogenase level ≥1000 IU/L. Patients who had ≥3 of the 5 adverse factors (45%) had a median survival of 2 to 3 months and CR rates of 8% to 15%. Achieving CR was associated independently with improved survival in a landmark multivariate analysis (P < .0001; hazard ratio, 0.40; 95% confidence interval, 0.03‐0.72).

CONCLUSIONS:

The current analyses identified a subset of adults patients ALL in first salvage for whom standard therapies were associated with an extremely poor outcome. The results also confirmed the importance of achieving CR to attain improved survival. Cancer 2010. © 2010 American Cancer Society.     

Efficacy and Safety of Blinatumomab for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Systemic Review and Meta-Analysis

ObjectiveThe aim was to evaluate the efficacy and safety of blinatumomab monotherapy for the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL).MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched to collect clinical studies related to blinatumomab. The primary outcome measures were complete remission (CR), and minimal residual disease (MRD) response. Prognostic indicators included overall survival (OS) and relapse-free survival time (RFS). Grade ≥3 adverse reactions were mainly analyzed for safety, including cytokine release syndrome (CRS), neurological events and hematological toxicity. The heterogeneity was quantified by I² statistic, which reflected the proportion of the true heterogeneity to the variance of the total effect size. Studies were considered heterogeneous if the I² statistic was greater than 50%, and conversely, studies were homogeneous.ResultsA total of 18 studies involving 1,373 patients were included. The analysis results showed a CR rate of 54% (95%CI:44%-64%) and an MRD response rate of 43% (95%CI:34%-51%). The CR rate was higher in patients with bone marrow (BM) blast <50% than in patients with BM blast ≥50% (71% vs. 34%). The median OS and RFS were 8.16 months (95%CI:6.64-9.69) and 6.02 months (95%CI:4.63-7.41), respectively. For safety analysis, the incidence of grade ≥3 adverse events (AEs) was 80% (95%CI:72%-88%), the incidence of grade ≥3 neurological toxicity was 7% (95%CI:4%-11%), and the incidence of grade ≥3 CRS was 3% (95%CI:2%-5%). However, the mixture of retrospective and prospective studies led to heterogeneity to some extent in this meta-analysis.ConclusionBlinatumomab is effective in the treatment of R/R B-ALL with a controlled occurrence of AEs and a reliable safety profile.     

Dramatic dietary fat reduction is feasible for breast cancer patients: Results of the randomised study, WINS (UK) – Stage 1

Introduction

The influence of dietary fat on breast tumour growth¹ and, more recently, on treatment outcomes, ^{[2] and [3]} suggests an important role for dietary advice in the future health of breast cancer patients. The Women’s Intervention Nutrition Study (UK) – Stage 1 assessed the feasibility of achieving and maintaining a ≥50% reduction in reported fat intake in postmenopausal, early stage breast cancer patients in the UK.

Method

This study recruited patients in South-east England between 2000 and 2005. They were randomly allocated into two groups. Group 1 (n = 54), received specific dietary counselling to halve their reported fat intake and maintain this low fat intake. Group 2 (n = 53) received healthy eating advice only. Dietitian-led group sessions provided support for women in both groups over 2 years.⁴ Validated four-day diaries were used to measure intake. Data analysis used Generalised Linear Model (GLM) for repeated measures and logistic regression.

Results

A significantly greater proportion of women in Group 1 reported a fat intake reduction of ≥50% at 3 months (p < .001) and 24 months (p < .001) than in Group 2. The size of the effect of active dietary counselling was 37% at 3 months (95%CI: 21–54%) and 35% at 24 months (95%CI: 17–53%). Mean fat intake was halved at 3 months and 24 months in Group 1 only.

Conclusion

Demonstrating such feasibility is a key step towards defining diet’s role in the secondary prevention of breast cancer.     

Therapeutic exposures and pubertal testicular dysfunction are associated with adulthood milestones and paternity after childhood cancer

Background

Childhood cancer therapy may cause long-term effects. This cross-sectional study evaluated adulthood milestones in male childhood cancer survivors (CCS).

Methods

The study population comprised 252 male CCS with 6 to 42 years of survival diagnosed at the Children’s Hospital in Helsinki (1964–2000) at the age of 0 to 17 years. Sex-, age-, and area of residence–matched population controls were randomly selected from the Finnish national registries. Data on moving away from the parental home, marital status, offspring, and adoption in CCS were compared with the population controls. We analyzed the influence of chemotherapy and radiation exposures and testicular dysfunction (ever nontestosterone-substituted serum follicle stimulating hormone >15 IU/L, luteinizing hormone >15 IU/L, testosterone <2 ng/mL (5 nmol/L), need of testosterone replacement therapy, or testicular volume <12 mL at the end of puberty) during pubertal maturation on long-term social outcomes.

Results

CCS moved away from their parental home as frequently as population controls (97.8% vs. 98.5%, p = .45). CCS were less likely to marry or live in a registered relationship (46.4% vs. 57.5%, p < .001), especially when diagnosed at a young age (<4 years). Among those married, the probability of divorce was similar between CCS and population controls (27.4% vs. 23.8%, p = .41). Survivors were less likely to sire a child (38.5% vs. 59.1%, p < .001) and more likely to adopt (2% vs. 0.4%, p = .015). Lower probability of paternity was associated with hematopoietic stem cell therapy, testicular radiation dose >6 Gy, pubertal signs of testicular dysfunction (nontestosterone-substituted serum follicle stimulating hormone >15 IU/L, luteinizing hormone  >15 IU/L, testosterone <2 ng/mL (5 nmol/L), or need of testosterone replacement therapy during puberty, or testicular volume <12 mL at the end of puberty) or azoospermia after puberty.

Conclusions

This study emphasizes the value of pubertal monitoring of testicular function to estimate future probability of paternity. If no signs of dysfunction occurred during pubertal follow-up, paternity was comparable to population controls. Testicular radiation dose >6 Gy appeared to be the strongest risk factor for decreased paternity.

Plain Language Summary

• Treatment with intensive therapies, including hematopoietic stem cell therapy, testicular radiation dose >6 Gy, and signs of testicular dysfunction, during puberty are important risk factors for lower rates of fertility.
• Intensive therapies and testicular dysfunction itself do not similarly hamper psychosocial milestones in adulthood; cancer diagnosis at a very young age (<4 years) lower the probability of marriage.
• This study accentuates the importance of monitoring of pubertal development, emphasizing on testicular function, not only sperm analysis, to estimate future fertility among male childhood cancer survivors.