2-[18F]FDG-PET/CT in Cancer of Unknown Primary Tumor-A Retrospective Register-Based Cohort Study.

We investigated the impact of 2-[18F]FDG-PET/CT on detection rate (DR) of the primary tumor and survival in patients with suspected cancer of unknown primary tumor (CUP), comparing it to the conventional diagnostic imaging method, CT. Patients who received a tentative CUP diagnosis at Odense University Hospital from 2014-2017 were included. Patients receiving a 2-[18F]FDG-PET/CT were assigned to the 2-[18F]FDG-PET/CT group and patients receiving a CT only to the CT group. DR was calculated as the proportion of true positive findings of 2-[18F]FDG-PET/CT and CT scans, separately, using biopsy of the primary tumor, autopsy, or clinical decision as reference standard. Survival analyses included Kaplan-Meier estimates and Cox proportional hazards regression adjusted for age, sex, treatment, and propensity score. We included 193 patients. Of these, 159 were in the 2-[18F]FDG-PET/CT group and 34 were in the CT group. DR was 36.5% in the 2-[18F]FDG-PET/CT group and 17.6% in the CT group, respectively (p = 0.012). Median survival was 7.4 (95% CI 0.4-98.7) months in the 2-[18F]FDG-PET/CT group and 3.8 (95% CI 0.2-98.1) in the CT group. Survival analysis showed a crude hazard ratio of 0.63 (p = 0.024) and an adjusted hazard ratio of 0.68 (p = 0.087) for the 2-[18F]FDG-PET/CT group compared with CT. This study found a significantly higher DR of the primary tumor in suspected CUP patients using 2-[18F]FDG-PET/CT compared with patients receiving only CT, with possible immense clinical importance. No significant difference in survival was found, although a possible tendency towards longer survival in the 2-[18F]FDG-PET/CT group was observed.

Addressing Chemotherapy-Induced Peripheral Neuropathy Using Multi-Frequency Vibrometry and Patient-Reported Outcomes.

(1) The study evaluated correlations between multi-frequency vibrometry (MF-V) and the measure of chemotherapy-induced peripheral neuropathy developed by the European Organization for the Research and Treatment of Cancer (CIPN18). (2) Patients with cancer scheduled to undergo treatment with capecitabine and oxaliplatin (CAPOX) or carboplatin and paclitaxel (Carbo-Tax) were recruited in a prospective, observational study with MF-V and the CIPN18 from baseline to one year after end of treatment. (3) The study recruited 31 evaluable patients. All MF-V measurements correlated significantly with the CIPN18 scores (r = 0.25−0.48, p > 0.003), with a low frequency (32 Hz) from metatarsals showing the best correlation coefficients (0.059 Z-score per CIPN18 point change, r = 0.48, CI-95 = [0.32; 0.60], p > 0.0001). The largest change in MF-V scores from baseline was seen in low-frequency VPTs taken from metatarsals at 8 Hz three months after end of treatment (from −0.26, CI-95 [−0.85, 0.38] to 1.15, CI-95 [0.53, 1.84]) for patients treated with oxaliplatin and at 32 Hz one year after end of treatment (from 0.09, CI-95 [−0.56, 0.77] to 0.88, CI-95 [0.34, 1.47]) for patients treated with paclitaxel. (4) Low-frequency vibration perception thresholds (8 and 32 Hz) correlated better with CIPN18 scores than high-frequency ones (128 and 250 Hz). If validated, this finding will advance CIPN pathophysiological understanding and inform the development of assessment methods.

The prevalence, distribution and impact of peripheral neuropathy among Danish patients with cancer - a population-based cross-sectional study.

BACKGROUND: Prevalence of peripheral neuropathy (PN) has been studied in patients undergoing treatment with taxanes, platinums and vinca alkaloids. The prevalence is unknown in the general oncological cancer population, characterized by advanced age, comorbidities and heterogeneous treatments. MATERIAL AND METHODS: A cross-sectional survey was administered to all adult patients, attending outpatient services at three Danish departments of oncology. The survey contained the EORTC-CIPN20, the EORTC-QLQ-C30, the GAD7 and PHQ9 questionnaires. A high PN symptom score was defined as a summary score ≥30 points on the CIPN20. P-values were adjusted for multiple testing. RESULTS: With an overall response rate of 83% (2839 patients), prevalence of PN was 17% overall, varying from 6 to 33% between diagnosis groups.A high score was more common among females (19 vs. 14%, p = .008), smokers (21 vs. 15%, p = .04), patients living alone (21 vs. 15%, p = .002) and patients using cannabis (29 vs. 15%, p < .001), as well as patients suffering from diabetes (26 vs. 16%, p < .001), cardiac heart disease (27 vs. 16%, p < .001), arthritis (32 vs. 15%, p < .001) or chronic obstructive pulmonary disease (25 vs. 16%, p = .01). High score patients were also older (69ys vs 67ys, p = .048) and more likely experiencing polypharmacy (OR = 3.38 [95% CI, 2.64;4.35]).Patients with a high CIPN20 symptom score scored worse on all EORTC QLQ-C30 function and symptom scales. The mean adjusted C30 SumScore difference was -18.66 ([95% CI, -20.31; -17.02], p < .001). CONCLUSION: Symptoms of PN are experienced widely across cancer groups in the oncology setting. PN symptoms were associated with clinically relevant worse health-related quality of life and with patient-related factors as living alone, various comorbidities, polypharmacy, and cannabis use.

Cannabis use among Danish patients with cancer: a cross-sectional survey of sociodemographic traits, quality of life, and patient experiences.

PURPOSE: Patients with cancer are using cannabis for self-treatment. The reasons, experienced effects, and prevalence of use are unknown in the European general oncological population. METHODS: Adult patients with cancer attending outpatient oncology clinics were invited to participate in a cross-sectional survey. The questionnaire consisted of sociodemographic questions, validated scales on quality of life, neuropathy, anxiety and depression as well as questions regarding use of cannabis. RESULTS: The overall response rate was 83% (2839 patients) and 13% of patients were using or had used cannabis during their treatment. Rate of use was higher in smokers (19% vs 11%, p adjusted 0.002), in patients in active cancer treatment (14% vs 10%, p adjusted = 0.02), and in patients with depression (19% vs 11%, adjusted p = 0.002). Cannabis use was also correlated with lower quality of life (EORTC C30 SumScore mean diff. = - 7.61, 95% CI = [- 9.69; - 5.53]). In total, 77% of users experienced at least one positive effect of cannabis, 18% experienced no effect, and 5% experienced other effects. At least one side effect was experienced by 33% of users. Management of pain and nausea were the primary reasons for initiating cannabis use (39% for both). Less nausea and better sleep were the most common effects experienced (26% for both). Oils for oral use were the most common route of administration (88%). CONCLUSION: Cannabis use among patients with cancer is prevalent and correlated with worse quality of life. Patients report using cannabis for symptom management and many experience relief of their symptoms. However, one third of patients experienced side effects.

Health-related quality of life of patients with haematologic cancer during COVID-19 and their opinions on telehealth consultations - a Danish single site cross-sectional survey.

INTRODUCTION: During the COVID-19 pandemic, high-risk patient groups might have practiced social distancing and sheltering, and hospitals may have changed or postponed treatments and examinations. We aimed to explore health-related quality of life (QoL) in patients with haematological diseases during the early phase of the pandemic and their acceptability of using telehealth. PATIENTS AND METHODS: We performed a cross-sectional survey among patients at the Department of Haematology, Odense University Hospital, Denmark. Eligible participants were patients receiving either active treatment or survivors in a follow-up program. The survey was open from 22 May to 13 June 2020. The survey contained questions on concerns and the impact of COVID-19 and acceptability on telehealth in addition to the assessment of health-related QoL. The later was assessed by the European Organisation for Research and Treatment of Cancer core QoL (EORTC QLQ-C30) questionnaire with the subdomains Global QoL, emotional functioning (EF) and social functioning (SF) being of primary interest. Further, anxiety during COVID-19 was assessed by use of an adapted version of the generalised anxiety disorder (GAD-7) questionnaire. RESULTS: 4420 patients were eligible to participate. The response rate was 53% (n = 2239) of which 37% where in a treatment program and 63% where in a follow-up program. The majority (80%) of patients were concerned about contracting COVID-19. The global QoL score (69.0, ±SD 22.6) was markedly lower than EF (84.5, ±SD 18.9) and SF (85.0, ±SD 23.4). Regression analysis showed that being concerned (a little, moderately, very, extremely) about contracting COVID-19 correlated with lower scores of global QoL (-3.86 to -22.76), EF (-3.81 to -26.41) and SF (-1.14 to -22.49). The GAD-7 score showed that approximately 20% of patients had symptoms of COVID-19 associated generalised anxiety. Finally, 67% of the patients were positive towards replacing face-to-face consultancies with phone calls, but video consultations were less preferred (47%). CONCLUSION: Danish patients with haematological cancer presented with low global QoL during the early phase of COVID-19, and 20% of the patients showed symptoms of generalised anxiety. Patients were overall positive towards the implementation of telehealth consultancies.

Quality of life in patients with cancer during the COVID-19 pandemic - a Danish cross-sectional study (COPICADS).

BACKGROUND: The COVID-19 pandemic is an international public health crisis. The risk of getting an infection with COVID-19 might impact the emotional well-being in patients with cancer. The aim of this study was to investigate quality of life (QoL) for patients with cancer during the COVID-19 pandemic. PATIENTS AND METHODS: A cross-sectional survey, including questions about demographics, concerns of COVID-19 impact on cancer treatment and outpatient clinic visits, and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was sent to patients with cancer at the Department of Oncology, Odense University Hospital, Denmark. The survey was open from 15th May to 29th May 2020, and 4.571 responded. Results were compared to the Danish 'Barometer Study' conducted by the Danish Cancer Society to elucidate experiences with the Danish healthcare system prior to COVID-19 pandemic. RESULTS: In total, 9% of patients with cancer had refrained from consulting a doctor or the hospital due to fear of COVID-19 infection, and 80% were concerned about contracting COVID-19 to some extent. Seventeen patients were tested positive for COVID-19. The mean global QoL and emotional functioning (EF) scores were 71.3 and 82.8, respectively. In comparison to the 'Barometer Study', no clinical significant differences in QoL and EF scores were observed. Multivariate analysis demonstrated that being 'Concerned about contracting corona-virus' was correlated with lower QoL and EF scores. Factors associated with being concerned of contracting COVID-19 were comorbid conditions, incurable cancer, receiving medical cancer treatment and female gender. CONCLUSION: Danish patients with cancer during the COVID-19 pandemic did not have lower scores of QoL and emotional functioning compared to the Danish 'Barometer Study'. However, the study suggests that concerns of contracting COVID-19 was correlated with lower scores of QoL.

Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives.

BACKGROUND: Chemotherapy with taxanes and platinum compounds has resulted in substantial survival benefits both in adjuvant and metastatic settings. However, as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which may result in discontinuation of treatment, and if it persists after treatment completion, has a negative impact on quality of life (QoL). RESULTS: Symptoms of CIPN are sensory, like pain, numbness, and tingling, typically located in the hands and feet. For oxaliplatin, there is an acute form of CIPN, resulting in paraesthesias in the mouth and throat during or shortly after the infusion triggered by exposure to cold. Risks factors for CIPN include preexisting neuropathy, either from treatment with other neurotoxic agents, or from comorbid conditions. The incidence of CIPN is related to dose per cycle, cumulative dose, and duration of infusion. While cisplatin-induced neuropathy is irreversible, CIPN induced by taxanes may persist for several years in about 30% of patients. Evidence from the literature is suggestive that CIPN is likely to be negatively associated with QoL. No agents have been identified to be recommended for the prevention of CIPN. For treatment of CIPN, the best available data supports a moderate recommendation for treatment with duloxetine and evidence is inconclusive regarding the use of tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine. CONCLUSION: Research is still needed to predict which patients are at high risk of developing CIPN during treatment and in whom CIPN will persist after completion of chemotherapy.

Docetaxel-induced neuropathy: a pharmacogenetic case-control study of 150 women with early-stage breast cancer.

BACKGROUND: Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in GSTP1 and ABCB1 on DIPN. MATERIAL AND METHODS: DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two polymorphisms in GSTP1 and three in ABCB1 were selected for the primary analysis, and a host of other candidate genes was explored and compared between 75 patients with clinician-reported DIPN grade ≥ 2 and 75 patients without DIPN. RESULTS: Patients with the genetic variants GSTP1 rs1138272 C/T or T/T (114Ala/114Val or 114Val/114Val) genotype had an adjusted odds ratio of 3.82; 95% confidence interval 1.34-11.09 of developing DIPN. This result was confirmed in both analysis of cumulated docetaxel dose and haplotype analysis. None of the explorative genes investigated were significantly correlated with DIPN. Patients with a BMI ≥ 30 were five-fold more likely to have DIPN than patients with BMI < 25. CONCLUSION: We found that GSTP1 Ala114Val polymorphism is associated with occurrence of DIPN. This supports the theory that oxidative stress is involved in DIPN pathophysiology. If confirmed, this may be helpful in the risk assessment of DIPN and perhaps help to achieve better management of neurotoxicity.

Persistent pain, sensory disturbances and functional impairment after adjuvant chemotherapy for breast cancer: cyclophosphamide, epirubicin and fluorouracil compared with docetaxel + epirubicin and cyclophosphamide.

BACKGROUND: Taxanes used in adjuvant therapy for breast cancer are neurotoxic, and thereby being a potential risk factor for persistent pain after breast cancer treatment (PPBCT) and sensory disturbances. The purpose was to compare patients treated with cyclophosphamide, epirubicin and fluorouracil (CEF) and cyclophosphamide and epirubicin + docetaxel (CE + T) in relation to PPBCT, sensory disturbances, peripheral sensory disturbances and functional impairment. MATERIAL AND METHODS: A comparative nationwide cross-sectional questionnaire study on two cohorts treated with CEF respectively CE + T, based on the Danish Breast Cancer Cooperative Groups database. INCLUSION CRITERIA: women treated with chemotherapy as adjuvant treatment for primary breast cancer, age 18-69 years, without recurrence. RESULTS: One thousand two hundred and forty-one patients allocated to CEF in 2005-2006 and 1652 patients allocated to CE + T in 2007-2008 were included. Six hundred and sixty-four (53%) with CEF and 861 (53%) patients with CE + T reported pain. In the multivariate analysis including available risk factors, CE + T did not confer an increased risk of PPBCT, OR 0.95 (95% CI 0.81-1.11), p = 0.52, compared to CEF. Patients treated with CE + T had a lower risk of sensory disturbances in the area of surgery compared with CEF, OR 0.75 (95% CI 0.62-0.90), p = 0.002. More CE + T patients reported peripheral sensory disturbances in the hands, OR 1.56 (95%CI 1.27-1.92), p < 0.0001, and in the feet, OR 2.0 (95% CI 1.66-2.42) p < 0.0001, compared to CEF. There was no difference in functional impairment (p = 0.62). CONCLUSION: Docetaxcel as adjuvant treatment for breast cancer does not increase the risk of PPBCT, sensory disturbances in the surgical area or functional impairment, but increase risk for peripheral sensory disturbances.

TAXTOX - a retrospective study regarding the side effects of docetaxel given as part of the adjuvant treatment to patients with primary breast cancer in Denmark from 2007 to 2009.

BACKGROUND: In 2007 docetaxel was introduced as part of the adjuvant setting offered to high risk breast cancer patients in Denmark. Meta-analyses had shown that taxane-containing chemotherapy reduced the relative risk of relapse and death by 20-30%, apparently with moderate side effects. The treatment was given as three cycles of cyclophosphamide (600 mg/m(2)) and epirubicin (90 mg/m(2)) followed by three cycles of docetaxel (100 mg/m(2)). Because of an apparent high incidence of side effects, especially febrile neutropenia (FN) and non-hematologic side effects, the DBCG (The Danish Breast Cancer Cooperative Group) initiated a retrospective study of adverse reactions to the newly introduced regime and all patients were offered primary prophylaxis with growth factors (G-CSF) pr 1/1-2008. MATERIAL AND METHODS: Two medical doctors examined available journals and nurse charts from the 13 oncology departments in Denmark, and graded all side effects according to NCI CTC version 2.0. To be enrolled, the patients should have received three cycles of EC and at least one cycle of docetaxel. The side effects were investigated before and after routine use of G-CSF. RESULTS: One thousand one hundred and forty-three patients entered the study. In 2007 (before G-CSF) the incidence of FN was 25% and 90.6% of the patients completed the planned treatment. In 2008 (after the introduction of G-CSF) the incidence of FN was 10% and 94.5% completed the treatment. The incidence of non-hematological adverse events, in 2007 and 2008 combined, was for neuropathy 35%, mucositis 75%, muscle and joint pain 53%, skin rash 25% and fatigue 43% (all grades). CONCLUSION: The introduction of G-CSF was justified because of the high incidence of FN. However, it could not have been predicted after reviewing the published literature. The incidence of non-hematological adverse events had been reported in some, but not all adjuvant taxanes studies. In the future, focus should be more on the side effects, especially when introducing new toxic systemic regimes.