Identifying the subtypes of cancer-related fatigue: results from the population-based PROFILES registry

Purpose

Little research has been done to identify possible cancer-related fatigue (CRF) subtypes and to classify cancer survivors accordingly. We aimed to identify CRF subtypes in a large population-based sample of (long term) stage I–III colorectal cancer survivors. We also identified factors associated with the CRF subtypes.

Methods

Respondents completed the Multidimensional Fatigue Inventory and other validated questionnaires on anxiety and reduced positive affect (anhedonia), sleep quality, and lifestyle factors (body mass index and physical activity). Latent class analysis was used to derive the CRF subtypes. Factors associated with the derived CRF subtypes were determined with multinomial logistic regression.

Results

Three CRF classes were identified: class 1 (no fatigue and distress, n = 644, 56%), class 2 (low fatigue, moderate distress, n = 256, 22%), and class 3 (high fatigue, moderate distress, n = 256, 22%). Multinomial logistic regression results show that survivors in class 3 were more likely to be female, were treated with radiotherapy, have comorbid diabetes mellitus, and be overweight/obese than survivors in class 1 (reference). Survivors in classes 2 and 3 were also more likely to have comorbid heart condition, report poorer sleep quality, experience anhedonia, and report more anxiety symptoms when compared with survivors in class 1.

Conclusions

Three distinct classes of CRF were identified which could be differentiated with sleep quality, anxiety, anhedonia, and lifestyle factors.

Implications for cancer survivors

The identification of CRF subtypes with distinct characteristics suggests that interventions should be targeted to the CRF subtype.

     

Randomized controlled pilot trial of mindfulness-based stress reduction for breast and colorectal cancer survivors: effects on cancer-related cognitive impairment

Purpose

Cancer-related cognitive impairment (CRCI) is a common, fatigue-related symptom that disrupts cancer survivors’ quality of life. Few interventions for CRCI exist. As part of a randomized pilot study targeting cancer-related fatigue, the effects of mindfulness-based stress reduction (MBSR) on survivors’ cognitive outcomes were investigated.

Methods

Breast and colorectal cancer survivors (n?=?71) with moderate-to-severe fatigue were randomized to MBSR (n?=?35) or a fatigue education and support (ES; n?=?36) condition. The Attentional Function Index (AFI) and the Stroop test were used to assess survivors’ cognitive function at baseline (T1), after the 8-week intervention period (T2), and 6 months later (T3) using intent-to-treat analysis. Mediation analyses were performed to explore mechanisms of intervention effects on cognitive functioning.

Results

MBSR participants reported significantly greater improvement on the AFI total score compared to ES participants at T2 (d?=?0.83, p?=?0.001) and T3 (d?=?0.55, p?=?0.021). MBSR also significantly outperformed ES on most AFI subscales, although both groups improved over time. MBSR produced greater Stroop accuracy rates relative to ES at T2 (r?=?0.340, p?=?0.005) and T3 (r?=?0.280, p?=?0.030), with improved accuracy over time only for the MBSR group. There were no significant differences in Stroop reaction time between groups. Improvements in mindfulness mediated the effect of group (e.g., MBSR vs. ES) on AFI total score at T2 and T3.

Conclusions

Additional randomized trials with more comprehensive cognitive measures are warranted to definitively assess the efficacy of MBSR for CRCI.

Implications for Cancer Survivors

This pilot study has important implications for all cancer survivors as it is the first published trial to show that MBSR offers robust and durable improvements in CRCI.

     

Short stature in retinoblastoma survivors: a cross-sectional study of 138 patients

Purpose

Short stature has been reported in pediatric cancer survivors. Data on retinoblastoma survivors are limited. We conducted a cross-sectional study to assess the height in retinoblastoma survivors.

Method

The recorded height was compared with median height for age and sex as per the Indian Academy of Pediatrics. Z-score less than ?2 was considered short statured.

Result

Thirty percent of the survivors were short statured. The mean height was shorter than the mean 50th percentile height (119.7 ± 14.8 vs 128.7 ± 15 cm, p < 0.001). Previous chemotherapy showed a trend toward association (p = 0.09).

Conclusion

Short stature affects a significant number of retinoblastoma survivors.

     

Impact of tissue-based genomic profiling on clinical decision making in the management of patients with metastatic breast cancer at academic centers

Purpose

The aim of this study is to elucidate the role of taxanes on cognition when they are administered as a part of the treatment with a fluorouracil, epirubicin and cyclophosphamide (FEC) regimen for breast cancer (BC).

Methods

Two groups of women (n = 51) with a novel diagnostic of BC that were treated with a combination of FEC alone (6 cycles of FEC) or with taxanes (4 cycles of FEC plus 8 cycles of taxanes) were compared at three moments: before chemotherapy, after its completion (short-term evaluation) and at a mean of 74.5 weeks from baseline as a long-term evaluation.

Results

Both groups showed worsening in tests of attention and executive functions on the short-term assessment, with the group treated with taxanes showing more number of affected cognitive measures at this time point, including verbal learning and speed measures. At the long-term evaluation, cognitive dysfunction was still found in attention and executive functions in both groups.

Conclusion

Our results suggest that chemotherapy for BC with a FEC regimen can have a negative effect on cognition. Acute deficits seem to be larger when taxanes are added, but treatment seems to affect cognition also at long term.

     

Aggressive fibromatosis response to tamoxifen: lack of correlation between MRI and symptomatic response

Background

One of the commonly used systemic agents for the treatment of aggressive fibromatosis is the anti-oestrogen drug tamoxifen. However, data on efficacy and optimum methods of response assessment are limited, consisting mainly of small case series and reports.

Methods

A retrospective database was used to identify consecutive patients diagnosed with aggressive fibromatosis (AF) and treated with tamoxifen plus/minus non-steroidal anti-inflammatory drugs at our tertiary referral centre between 2007 and 2014. MRI and symptom changes were recorded.

Results

Thirty-two patients (13 male 19 female, median age 41 years) were included. Median duration of treatment with tamoxifen was 316 days. Of 9 patients with progressive disease by RECIST 1.1 (28%): 4 patients experienced worsening symptoms; 3 patients had improved symptoms and 2 had no change in symptoms. Of 22 patients with stable disease (69%): 11 had no change in symptoms; 6 had improved symptoms and 5 patients had worsening symptoms. One patient achieved a partial response with improved symptoms.

Conclusions

No relationship was identified between symptomatic benefit and response by RECIST 1.1 on MRI. Prospective studies in AF should incorporate endpoints focusing on patient symptoms.

     

Identification of adverse events that have a negative impact on quality of life in a clinical trial comparing docetaxel versus S-1 with cisplatin in lung cancer

Purpose

In the CATS (Cisplatin And TS-1) randomized trial comparing cisplatin plus either docetaxel (DP arm) or TS-1 (SP arm) in lung cancer, efficacy was found to be equivalent but the global quality of life (QOL) score was higher in the SP arm. The purpose of the current study was to identify which of the adverse events (AEs) contributed to the deterioration of QOL.

Methods

QOL and AE data from the CATS trial were used to quantitatively analyze the relationship between deterioration of QOL score and occurrence of AEs. Subtracted values of the QOL score from post-chemotherapy to pre-chemotherapy were fully compared between patients with or without each AE (Student’s t test, significance level = 0.001). Multivariate linear regression analysis was also performed. Analysis of variance was performed to identify whether grade of AE(s) might be significantly correlated with the deterioration of the QOL score (significance level of 0.05).

Results

As expected, gastrointestinal (GI) toxicities were associated with worsening of a variety of QOL items in both trial arms, detected by both univariate and multivariate analysis (p < 0.001 and p < 0.0001, respectively). Multivariate analysis unpredictably indicated that an increase in serum bilirubin level was the only AE that was uniquely associated with worsening of physical functioning (p = 0.0002), cognitive functioning (p < 0.0001), and financial problems (p = 0.0005) in the DP arm, although not in the SP arm. GI toxicities tended to be prolonged in the SP arm.

Conclusion

An increase in serum bilirubin level may contribute to the worse global QOL of subjects in the DP arm in the CATS trial. The method we used here may be a unique approach to identify unpredictable AE(s) that worsen the QOL of patients treated by chemotherapy.

     

Expression Analysis of Survivin and XIAP in Gallbladder Cancer: a Case-control Study in Indo-Gangetic Plain

Purpose

Gallbladder cancer is a highly mortal disease with poor prognosis because of late presentation of disease. Survivin and X-linked inhibitor of apoptosis (XIAP) are one of the two important members of inhibitors of apoptosis. Thus, this study aimed to look at the expression of Survivin and XIAP in gallbladder cancer patients.

Methods

Survivin and XIAP expression were investigated in tissues of gallbladder cancer patients (40 cases) and compared with cholelithiasis as control (40 cases) by using immunohistochemistry. Their expression was correlated with clinicopathological parameters.

Results

Significantly higher (p < 0.05), Survivin protein was expressed in gallbladder cancer (n = 67.5%) than control (n = 35%). But it did not show any significant association with any of the clinicopathological parameter while XIAP was not expressed in the GBC patients (p > 0.05).

Conclusion

Overexpression of Survivin in gallbladder cancer suggests its possible role and association with poor prognosis. But XIAP has not been found to be associated with gallbladder carcinogenesis.

     

Ionizing radiation exposure as a result of diagnostic imaging in patients with lymphoma

Purpose

Survival rates among patients with lymphoma continue to improve. Strategies aimed at reducing potential treatment-related toxicity are increasingly prioritized. While radiological procedures play an important role, ionizing radiation exposure has been linked to an increased risk of malignancy, particularly among individuals whose cumulative radiation exposure exceeds a specific threshold (75 millisieverts).

Methods

Within this retrospective study, the cumulative radiation exposure dose was quantified for 486 consecutive patients with lymphoma.

Results

The median estimated total cumulative effective dose (CED) of ionizing radiation per subject was 69 mSv (42–118). However, younger patients (under 40 years) had a median CED of 89 mSv (55–124).

Conclusion

This study highlights the considerable radiation exposure occurring among patients with lymphoma as a result of diagnostic imaging. To limit the risk of secondary carcinogenesis, consideration should be given to monitoring cumulative radiation exposure in individual patients as well as considering imaging modalities, which do not impart an ionizing radiation dose.

     

Engagement and experience with cancer-related follow-up care among young adult survivors of childhood cancer after transfer to adult care

Purpose

Young adult survivors (YAS) of childhood cancer require annual adult-focused, cancer-related follow-up given their risk for late effects of treatment. This study describes perception of and engagement with adult-focused, cancer-related follow-up care and general health care among YAS formally transferred to adult care from pediatric survivorship care.

Methods

YAS transferred from pediatric survivorship care in the prior 1–5 years completed measures indicating engagement with cancer-related follow-up care, other health care utilization, content of communication by providers, quality of cancer-related care, and satisfaction with health care in the prior year.

Results

Eighty YAS (M age?=?27.7 years, M time since diagnosis?=?10.4 years) participated. Just over half of YAS surveyed (n?=?44, 55 %) endorsed continuing cancer-related follow-up care since transfer. Those with cancer-related follow-up endorsed seeing subspecialty survivorship providers (n?=?16, 44 %) and primary care providers (n?=?22, 50 %) or utilizing a shared care model (n?=?6, 14 %). About a third of YAS endorsed seeing subspecialists (n?=?29, 36 %) or using other support services (n?=?22, 27 %). YAS-perceived content of communication varied significantly depending on care model with less cancer-related content being discussed by primary care providers, though perceived quality of cancer-related care and satisfaction with health care was generally favorable.

Conclusions

YAS report less than optimal engagement in cancer-related follow-up care and communication in their health care encounters.

Implications for Cancer Survivors

Young adult survivors should receive anticipatory guidance about expectations for delivery and content of adult-focused cancer-related follow-up care.

     

Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial

Purpose

Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) frequently occur in women being treated for breast cancer. Prior studies suggest high prevalence of vitamin D deficiency in breast cancer patients with musculoskeletal (MS) pain. We conducted a randomized, placebo-controlled trial to determine if 30,000 IU vitamin D3 per week (VitD3) would prevent worsening of AIMSS in women starting adjuvant letrozole for breast cancer.

Methods

Women with stage I–III breast cancer starting adjuvant letrozole and 25(OH)D level ≤40 ng/ml were eligible. All subjects received standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 and were randomized to 30,000 IU oral VitD3/week or placebo. Pain, disability, fatigue, quality of life, 25(OH)D levels, and hand grip strength were assessed at baseline, 12, and 24 weeks. The primary endpoint was incidence of an AIMSS event.

Results

Median age of the 160 subjects (80/arm) was 61. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 weeks, and 31 at 24 weeks in the placebo arm and 22, 53, and 57 in the VitD3 arm. There were no serious adverse events. At week 24, 51% of women assigned to placebo had a protocol defined AIMSS event (worsening of joint pain using a categorical pain intensity scale (CPIS), disability from joint pain using HAQ-II, or discontinuation of letrozole due to MS symptoms) vs. 37% of women assigned to VitD3 (p = 0.069). When the brief pain inventory (BPI) was used instead of CPIS, the difference was statistically significant: 56 vs. 39% (p = 0.024).

Conclusions

Although 30,000 IU/week of oral vitamin D3 is safe and effective in achieving adequate vitamin D levels, it was not associated with a decrease in AIMSS events based on the primary endpoint. Post-hoc analysis using a different tool suggests potential benefit of vitamin D3 in reducing AIMSS.

     

Relationships between sunitinib plasma concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma

Background

The aim was to investigate the relationships between total sunitinib plasma concentrations (sunitinib plus its active metabolite; N-desethyl sunitinib) and clinical outcomes in Japanese patients with metastatic renal cell carcinoma (mRCC).

Methods

Twenty patients with mRCC were enrolled following treatment with sunitinib. To assess safety, the total sunitinib concentration range up to discontinuation of treatment and dosage reduction associated with adverse events within 6 weeks from initiating administration were analyzed. The longest administered sunitinib dosage was defined as the maintenance dose, and the relationship between total sunitinib concentration at the maintenance dosage and sunitinib efficacy was investigated.

Results

Total sunitinib concentration was significantly higher in patients who discontinued treatment or had dosage reduction due to adverse events within 6 weeks after initiation of sunitinib than in patients who continued treatment with the initial dosage. The time to treatment failure, progression-free survival, and overall survival were better in patients with total sunitinib concentrations <?50 ng/mL than in those with concentrations ≥?50 ng/mL.

Conclusions

The present study demonstrated that the effective range of total sunitinib concentration in Japanese patients with mRCC was lower than 50–100 ng/mL which was previously reported. These results indicate that therapeutic drug monitoring could maintain the therapeutic effect of sunitinib while minimizing adverse events by personalizing sunitinib dosages for Japanese patients with mRCC.

     

Stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer

Purpose

To investigate whether bone metastases-directed stereotactic body radiation therapy (SBRT) delays the emergence of castration resistance in patients with oligometastatic prostate cancer (OPC).

Methods and material

OPC is usually managed with androgen deprivation therapy (ADT). Migration to castration-resistant prostate cancer will inevitably occur in the majority of these patients. There are several strategies aimed to delay the emergence of castration resistance including intermittent ADT, second generation antiandrogens (abiraterone, enzalutamide) or metastases-directed SBRT. The present report describes two cases of patients with OPC that received SBRT 24 Gy/3Rx to the solitary bony lesion after ADT failure.

Results

Both cases showed complete and durable biochemical response for 13 and 17 months, respectively.

Conclusions

SBRT can be used to delay the emergence of castration resistance and the need for systemic therapy when used after ADT failure.

     

Bone marrow trephine biopsy involvement by lymphoma: pattern of involvement and concordance with flow cytometry,in 10 years from a single institution

Purpose

To evaluate the features of bone marrow (BM) biopsy involvement by lymphoma, pattern of infiltration, morphological analysis and flow cytometry were reviewed at all lymphoma patients over a period of 10 years.

Methods/patients

413 cases were included in the study if BM biopsy slides were available. Only 356 patients had both BM trephine biopsy and flow cytometry.

Results

The most frequent subtype was diffuse large B cell (31.2 %), followed by follicular lymphoma (18.9 %). The predominant pattern was mixed (nodular-interstitial) (9.2 %). Morphological marrow infiltration was found in 138 cases, and flow cytometry identified 117 cases with BM involvement. A concordance between the two methods was detected in 305 cases (85.7 %). There was discordance in 51 cases (14.3 %): morphology positive/FC negative in 33 cases and morphology negative/FC positive in 18.

Conclusions

Flow cytometry is slightly more useful in detecting involvement when the BM is affected, but this finding is not conclusive.

     

Breast and cervical cancer screening among Hispanic subgroups in the USA: estimates from the National Health Interview Survey 2008, 2010, and 2013

Purpose

This study examined patterns in mammography and Pap test use across and within subpopulations of Hispanic women.

Methods

Based on data from the National Health Interview Survey (2008, 2010, and 2013), we estimated the proportion of Hispanic women reporting testing for breast and cervical cancer for specific subgroups. We examined test use by demographic characteristics using Chi-square tests.

Results

Overall, the proportion of women aged 50–74 years who reported a mammogram within the past 2 years did not differ significantly across Hispanic subgroups. Among publically and uninsured women, however, proportions of mammography utilization varied significantly across Hispanic subgroups. The proportion of women aged 21–65 years who received a Pap test within the past 3 years differed significantly across Hispanic subgroups.

Conclusions

Among subgroups of Hispanic women, patterns in mammography and Pap test use vary by insurance status, length of US residency, and type of screening. Certain subgroups of Hispanic women may benefit from culturally tailored efforts to promote breast and cervical cancer screening.

     

Do patients with metastatic urothelial carcinoma benefit from docetaxel as second-line chemotherapy?

Purpose

To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy.

Methods

Between May 2005 and June 2008, we retrospectively analyzed the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m² every 21 days for unfit patients or (2) docetaxel 75 mg/m² every 21 days for fit patients.

Results

Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event.

Conclusions

This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.

     

Correlation of FANCM expression with clinical factors in luminal B breast cancer

Background

The genotype of Fanconi Anemia complementation group M (FANCM) was previously found to be associated with breast cancer risk in several populations. Here, we studied the expression of FANCM and its correlation with clinical characteristics in Chinese patients with breast cancer.

Methods

We performed an immunohistochemical study of FANCM protein in clinical breast cancer tissues from 310 patients along with 44 adjacent tissues.

Results

FANCM protein level is lower in triple-negative breast cancer tissues than in other subtypes (P = 0.008). In addition, high FANCM expression correlated with pathology type IDC (P = 0.040), estrogen receptor positive (P < 0.001), progesterone receptor positive (P = 0.001), and low Ki-67 status (P = 0.003). Multivariate analysis revealed that FANCM status was an independent prognostic factor for overall survival (P = 0.017) in luminal B breast cancer.

Conclusions

FANCM levels are significantly associated with different subtypes of human breast cancer. Specifically, FANCM could play a role in the progression of luminal B breast cancer.

     

Fatigue and depressive symptoms improve but remain negatively related to work functioning over 18 months after return to work in cancer patients

Purpose

The aims of this study are to investigate the course of work functioning, health status, and work-related factors among cancer patients during 18 months after return to work (RTW) and to examine the associations between these variables and work functioning over time.

Methods

Data were used from the 18-month longitudinal “Work Life after Cancer” (WOLICA) cohort, among 384 cancer patients who resumed work. Linear mixed models were performed to examine the different courses during 18-month follow-up. Linear regression analyses with generalized estimating equations (GEE) were used to examine the associations and interactions.

Results

Cancer patients reported an increase of work functioning and a decrease of fatigue and depressive symptoms in the first 12 months, followed by a stable course between 12 and 18 months. Cognitive symptoms were stable during the first 18 months. Working hours increased and social support decreased during the first 6 months; both remained stable between 6 and 18 months. Fatigue, depressive, and cognitive symptoms were negatively associated with work functioning over time; working hours and supervisor social support were positively associated.

Conclusions

Interventions to improve cancer patients’ work functioning over time might be promising if they are aimed at reducing fatigue, depressive symptoms, cognitive symptoms, and encouraging supervisor social support.

Implications for Cancer Survivors

It is important to monitor cancer patients not only in the period directly after RTW but up to 18 months after RTW, allowing for timely interventions when needed.

     

Kurative perkutane Strahlentherapie des Prostatakarzinoms

Background

External beam radiotherapy (EBRT) is a curative therapeutic option in prostate cancer.

Percutaneous radiotherapy with curative intent

Patients with low risk can be cured with EBRT. For patients at intermediate risk, EBRT may be combined with androgen deprivation therapy (ADT) for 4 months. For patients at high risk, ADT should be administered for 2–3 years and the EBRT dose should be escalated. Hypofractionation is currently under intensive clinical investigation, but is currently not a clinical standard.

Recurrence

A recurrence after EBRT is defined as two prostate-specific antigen (PSA) values higher than nadir +2 ng/ml.

Adjuvant radiotherapy

Adjuvant EBRT is recommended after pT3 and/or R1 resection. In patients with lower stages or with more comorbidities, a PSA follow-up can be recommended with initiation of salvage EBRT only after increase of PSA (but preferably < 0.5 ng/ml).