Fatigue in people with localized colorectal cancer who do and do not receive chemotherapy: a longitudinal prospective study

BackgroundFatigue is associated with cancer and chemotherapy and may be sustained. Here, we describe a prospective longitudinal study evaluating fatigue and putative mechanisms in people with colorectal cancer (CRC).Patients and methodsPeople with localized CRC completed the Functional Assessment of Cancer Treatment-Fatigue (FACT-F) questionnaire at baseline (before chemotherapy, if given), 6, 12, and 24 months. Healthy controls (HCs) were assessed at the first three time points. Fatigue was defined by standardized FACT-F scores ≤68/100. Quality-of-life (QoL, assessed by the FACT-G questionnaire), affective, and cognitive symptoms were evaluated. Associations were sought between fatigue, baseline factors, and blood tests (including hemoglobin, cytokines, and sex hormones). Regression analyses, Fisher's exact tests, and Wilcoxon rank-sum tests assessed levels of fatigue at each time point and change in fatigue from baseline. A repeated-measures analysis investigated prognostic factors of fatigue across all time points.ResultsA total of 289 subjects with localized CRC (173 received chemotherapy) and 72 HCs were assessed. More CRC patients had fatigue than HCs at baseline (52% versus 26%, P < 0.001). Fatigue was increased in the chemotherapy (CTh) group at 6 months [CTh+ 70% versus CTh- 31% (P < 0.001), HCs 22%] and remained more common at 12 [CTh+ 44% versus CTh- 31% (P = 0.079)] and 24 months [CTh+ 39% versus CTh- 24% (P = 0.047)]. There was no significant difference between those not receiving chemotherapy and HCs at follow-up assessments. Fatigue was associated with poor QoL, affective and cognitive symptoms, but not consistently with cytokine levels. Predictors for sustained fatigue were baseline fatigue, treatment group, cognitive and affective symptoms, poorer QoL, and comorbidities.ConclusionsCRC patients have more fatigue than HCs at baseline. Fatigue peaks immediately after adjuvant chemotherapy, but remains common for 2 years in those who receive chemotherapy. Cognitive and affective symptoms, QoL, comorbidities, chemotherapy, and baseline fatigue predict for longer term fatigue.     

Choosing chemotherapy in patients with advanced urothelial cell cancer who are unfit to receive cisplatin-based chemotherapy

Transitional cell carcinoma of the urothelial tract is the second most common cancer of the genitourinary system and the fifth most common cancer in Western countries with more than 300,000 new cases per year worldwide. Following the introduction of cisplatin-based chemotherapy, median overall survival in patients with metastatic disease has doubled, demonstrating chemotherapy as an important treatment modality in advanced or metastatic disease. Patients 'unfit' to receive cisplatin-based chemotherapy are characterized by impaired renal function, impaired performance status, and/or comorbidity that preclude the use of cisplatin. In this review we summarize the different chemotherapeutic schemes, focusing on treatment options in cisplatin 'unfit' patients.     

Many men with castrate-sensitive metastatic prostate cancer should not receive chemotherapy

Criticism of ESMO prostate cancer guidelines     

Clinical significance of evaluating primary lesions in patients with gastric cancer who receive chemotherapy

Background  

In Western countries, the response of gastric cancer to chemotherapy is evaluated by assessing measurable metastatic lesions (MMLs) according to the response evaluation criteria in solid tumors (RECIST). In Japan, the response of primary lesions is assessed according to local Japanese criteria. We compared the response to chemotherapy as evaluated by these two sets of criteria.     

A tool for predicting breast carcinoma mortality in women who do not receive adjuvant therapy

BACKGROUND: Among the several proposed risk classification schemes for predicting survival in women with breast carcinoma, one of the most commonly used is the Nottingham Prognostic Index (NPI). The goal of the current study was to use a continuous prognostic model (similar to those that have already been demonstrated to possess greater predictive accuracy than risk group-based models in other malignancies) to predict breast carcinoma mortality more accurately compared with the NPI. METHODS: A total of 519 women who had been treated with mastectomy and axillary lymph node dissection at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1976 and 1979 met the following requirements for study inclusion: confirmation of the presence of invasive mammary carcinoma, no receipt of neoadjuvant or adjuvant systemic therapy, no previous history of malignancy, and negative lymph node status as assessed on routine histopathologic examination. Paraffin blocks were available for 368 of the 519 eligible patients. All available axillary lymph node tissue blocks were subjected to enhanced pathologic analysis. The competing-risk method was used to predict disease-specific death, and the accuracy of the novel prognostic model that emerged from this process was evaluated using the concordance index. Jackknife and 10-fold cross-validation predictions yielded by this new model were compared with predictions yielded by the NPI. RESULTS: Of the 348 women for whom complete data were available, 73 died of disease; the 15-year probability of breast carcinoma-related death was 20%. On the basis of these 348 cases, the authors developed a prognostic model that took patient age, disease multifocality, tumor size, tumor grade, lymphovascular invasion, and enhanced lymph node staining into account, and using competing-risks regression analysis, they found that this new model predicted disease-specific death more accurately compared with the NPI. CONCLUSIONS: The authors have developed a model for predicting breast carcinoma-specific death with improved accuracy. This tool should be useful in counseling patients with regard to their specific need for adjuvant therapy.     

Cognitive complaints and cognitive impairment following BEP chemotherapy in patients with testicular cancer

Introduction. There is growing concern that some cytotoxic regimens for cancer affect cognitive functioning. This study examined the prevalence of cognitive complaints and deficits in testicular cancer (TC) patients treated with the worldwide standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. Materials and methods. Seventy TC patients treated with BEP chemotherapy after surgery (S+CT) were examined with interviews and neuropsychological tests. These patients were compared with 57 TC patients treated with radiotherapy after surgery (S+RT) and with 55 TC patients that received surgery only (S). Patients were examined a median of 3 years after completion of treatment. Results. Thirty two percent of the S+CT patients reported cognitive complaints compared with 32% of the S+RT patients and 27% of the S patients (p=0.85). No differences in mean cognitive test performance were observed between the groups. On individual impairment scores, more S+CT patients showed cognitive dysfunction compared with S patients, but not compared with S+RT patients (S+CT versus S [p=0.038, OR=4.6, CI=1.1-19.7], S+CT versus S+RT [p=0.70, OR=0.8, CI=0.3-2.4] and S+RT versus S [p=0.070, OR=3.7, CI=0.8-15.7). Cognitive complaints were not related to cognitive test performance, but to emotional distress and fatigue. Discussion. Cognitive complaints are common among TC patients, independent of treatment modality. These complaints are related to emotional distress and fatigue and not to formal cognitive deficits. The finding of a small group of TC patients treated with chemotherapy exhibiting cognitive deficits should be confirmed in a prospective study before we can decide on its cause and relevance.     

Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

Background  Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. Methods  We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Results  Among the patients who received a trastuzumabcontaining regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2–14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0–45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Conclusion  Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases.     

High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy

AimAxillary dissection is increasingly forgone in early breast cancer patients with a clinically negative axilla. The GRISO 053 randomised trial recruited 435 patients of age over 45 years, tumour ?1.4 cm and clinically negative axilla, to assess the importance of axillary radiotherapy versus no axillary radiotherapy in patients not given axillary dissection. In the present study on a subgroup GRISO cases our aim was to assess the prognostic importance of tumour biological factors after more than 10 years of follow-up.MethodsWe retrospectively assessed biological factors in a subgroup of 285 GRISO cases (145 given axillary radiotherapy; 140 not given axillary radiotherapy) with complete biologic, therapeutic and follow-up information, using multivariable Cox proportional hazards regression modelling.ResultsOnly 10-year cumulative incidence of distant metastasis was lower in the axillary radiotherapy (1%) than no axillary radiotherapy arm (7%) (p = 0.037). Irrespective of study arm, hormone receptor positivity had significantly favourable effects on 10-year disease-free survival (DFS) and overall survival. human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes were associated with lower 10-year DFS (60% and 76%, respectively) than luminal A (96%) and B (91%) (p = 0.001). Ten-year DFS for high (?14%) Ki67 cancers was lower than for low Ki67 cancers (p = 0.027); however, this effect was mainly confined to the no axillary radiotherapy arm.Concluding statementFor patients with clinically node-negative small breast cancer not given axillary dissection, 10-year DFS is worsened by HER2 positivity, triple-negative phenotype and high Ki67. Axillary radiotherapy counteracts the negative prognostic effect of high Ki67 in patients not receiving axillary dissection.     

Molecular subtyping of early-stage breast cancer identifies a group of patients who do not benefit from neoadjuvant chemotherapy

The aim of this study was to analyze the correlation between the pathologic complete response (pCR) rate after neoadjuvant chemotherapy and long-term outcome (distant metastases-free survival [DMFS]) in patients with early-stage breast cancer using BluePrint and MammaPrint molecular subtyping versus clinical subtyping using immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) for the determination of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2). Data were analyzed from 437 patients in four neoadjuvant chemotherapy trials. BluePrint and MammaPrint outcomes were determined from 44K Agilent arrays, the I-SPY 1 data portal, or Affymetrix U133A arrays. The pCR rate differed substantially among BluePrint molecular subgroups: 6 % in Luminal A-type, 10 % in Luminal B-type, 47 % in HER2-type, and 37 % in Basal-type patients. In the Luminal A-type group (n = 90; including seven HER2-positive patients and eight triple-negative patients by IHC/FISH), the 5-year DMFS rate was 93 %. The pCR rate provided no prognostic information, suggesting these patients may not benefit from chemotherapy. Forty-three of 107 (40 %) HER2-positive patients were classified as Luminal-type by BluePrint and may have lower response rates to targeted therapy. Molecular subtyping identified 90 of 435 (21 %) patients as Luminal A-type (BluePrint Luminal-type/MammaPrint Low Risk) with excellent survival. The pCR rate provided no prognostic information. Molecular subtyping can improve the stratification of patients in the neoadjuvant setting: Luminal A-type (MammaPrint Low Risk) patients have a good prognosis with excellent survival and do not seem to benefit from chemotherapy. We observed marked benefit in response and DMFS to neoadjuvant treatment in patients subtyped as HER2-type and Basal-type. BluePrint with MammaPrint molecular subtyping helps to improve prognostic estimation and the choice of therapy versus IHC/FISH.     

Prognostic significance of thymidylate synthase in patients with metastatic colorectal cancer who receive protracted venous infusions of 5-fluorouracil

Background This study was conducted to evaluate the prognostic significance of thymidylate synthase (TS) expression in the tumor tissue of patients with metastatic colorectal cancer (CRC) who received protracted venous infusions of 5-fluorouracil (5-FU).Methods We retrospectively analyzed the prognostic value of TS expression as compared with other clinical prognostic factors in 57 patients with metastatic CRC.Results On univariate analysis, survival was significantly related to TS expression (low vs high; P = 0.0015), alkaline phosphatase (ALP) level (<300 vs 300IU/l; P = 0.0037), performance status (0 or 1 vs 2 or 3; P = 0.0073), and white blood cell count (<10000/mm³ vs 10000/mm³; P = 0.0001), with number of metastatic sites (1 vs 2; P = 0.06) approaching significance. On multivariate analysis, survival was significantly related to TS expression (hazard ratio [HR], 2.97) and ALP level (HR, 2.26).Conclusion In patients with metastatic CRC who received protracted venous infusions of 5-FU, TS expression was related to survival independently of other established clinical prognostic factors.     

Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy

BackgroundAlthough stromal tumor-infiltrating lymphocytes (sTILs) have been considered an important prognostic factor in early-stage triple-negative breast cancer (TNBC), there have been limited data on their prognostic value in the absence of adjuvant chemotherapy.Patients and methodsA pooled analysis was carried out using four cohorts of TNBC patients not treated with chemotherapy. sTILs were evaluated in the most representative tumoral block of surgical specimens. Cox proportional hazards regression models were used for invasive disease-free survival (iDFS), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors.ResultsWe analyzed individual data of 476 patients from 4 centers diagnosed between 1989 and 2015. Their median age was 64 years. The median tumor size was 1.6 cm and 83% were node-negative. The median level of sTILs was 10% (Q1−Q3, 4%−30%). Higher grade was associated with higher sTILs (P < 10⁻³). During follow-up, 107 deaths, and 173 and 118 events for iDFS and D-DFS were observed, respectively. In the multivariable analysis, sTILs obtained an independent prognostic value for all end points (likelihood ratio χ² = 7.14 for iDFS; P < 10⁻²; χ² = 9.63 for D-DFS, P < 10⁻²; χ² = 5.96 for OS, P = 0.015). Each 10% increment in sTILs corresponded to a hazard ratio of 0.90 [95% confidence interval (CI) 0.82 − 0.97] for iDFS, 0.86 (95% CI 0.77 − 0.95) for D-DFS, and 0.88 (95% CI 0.79 − 0.98) for OS, respectively. In patients with pathological stage I tumors with sTILs ≥30% (n = 74), 5-year iDFS was 91% (95% CI 84% to 96%), D-DFS was 97% (95% CI 93% to 100%), and OS was 98% (95% CI 95% to 100%).ConclusionsTILs add important prognostic information in systemically untreated early-stage TNBC patients. Notably, sTILs can identify a subset of stage I TNBC patients with an excellent prognosis without adjuvant chemotherapy.     

Objective and subjective cognitive impairment following chemotherapy for cancer: A systematic review

Evidence suggests that some cancer survivors experience cognitive difficulties following chemotherapy. However, perceived or subjective cognitive impairment is more frequently reported than prevalence revealed by objective assessments. The aim of this review was to examine the relationship between subjective and objective measures of cognitive impairment following treatment for cancer and to determine the number of studies that found a significant relationship between these measures of cognition. A comprehensive search for articles, published between 1980 and 2012, comparing subjective and objective cognition in cancer patients treated with chemotherapy was conducted. Of 818 potentially relevant articles, 23 studies met the inclusion criteria for the current review and one article was sourced from reference lists of included studies. Only eight of 24 included studies found a significant relationship between objective and subjective measures of cognitive performance. These studies were more likely to involve breast cancer patients and to assess the relationship between memory and perceived cognitive impairment. The failure to consistently find an association between subjective and objective measures of cognition could be explained by variations in assessment methods or the definition of impairment. Alternatively, objective and perceived cognitive impairment may be unrelated because perceived impairment may be an indicator of psychological distress rather than cognitive impairment. Despite these discrepancies, patients' perceptions of impairment are important due to its significant impact on quality of life. Further research is required to explore whether objective measures of everyday functioning better predict the impact of chemotherapy related cognitive impairment on daily functioning.     

A prognostic model in patients who receive chemotherapy for metastatic or recurrent gastric cancer: validation and comparison with previous models

Purpose  

To make up for the limitations of previous prognostic models, we developed and validated a model in patients with metastatic or recurrent gastric adenocarcinoma (AGC), and to compare with previous models.     

Optimising radiation treatment decisions for patients who receive neoadjuvant chemotherapy and mastectomy

Whereas randomised clinical trials have established which patients might benefit from postmastectomy radiation therapy after upfront surgery, no such data exist for guiding decisions on who might benefit from postmastectomy radiation therapy after upfront chemotherapy. Insight must be drawn from non-randomised data to provide such guidance. Early data suggest that both extent of disease at presentation and response to neoadjuvant chemotherapy predict the risk of locoregional recurrence, and can be used to tailor recommendations for postmastectomy radiation therapy. Randomised clinical trial data are needed to assess whether postmastectomy radiation therapy can be safely omitted in selected women with good response to neoadjuvant chemotherapy.