Oxaliplatin-Induced Neurotoxic Side Effects and Their Impact on Daily Activities: A Longitudinal Study Among Patients With Colorectal Cancer.

BACKGROUND: Oxaliplatin (OXA) is frequently used in the treatment of patients with colorectal cancer, and OXA-induced neurotoxic side effects are common. Reports on real-time patient-reported neurotoxic side effects and impact on the patient's daily activities are sparse in existing studies. OBJECTIVE: The aim of this study was to identify and assess patient-reported OXA-induced neurotoxic side effects and their impact on the patient's daily activities, during and after chemotherapy. METHODS: In a multicenter prospective longitudinal study, 46 chemo-naïve patients with colorectal cancer treated with postoperative adjuvant OXA-based chemotherapy were monitored during treatment and at 3-, 6-, 9-, and 12-month follow-ups. Patients were recruited from September 2013 to June 2016. In total, 370 Oxaliplatin-Associated Neurotoxicity Questionnaire responses were available for analysis. A mobile phone-based system was used to receive real-time assessments. RESULTS: All patients reported neurotoxic side effects and impact on daily activities during treatment. The side effects changed in character and body location over time and had an impact on the daily activities. CONCLUSIONS: The high prevalence of OXA-induced neurotoxic side effects significantly interfered with the patients' daily activities. We found significant differences between baseline data and follow-up time points for neurotoxicity, and the patients had not returned to baseline after 1 year. IMPLICATIONS FOR PRACTICE: The real-time assessment using mobile phone technology seems to be a valuable tool for monitoring patient-reported neurotoxicity and interventions for tailored care. Effectively identifying neurotoxicity and its impact on the patient's daily activities is important in supportive cancer care.

Neurotoxic Side Effects Early in the Oxaliplatin Treatment Period in Patients With Colorectal Cancer.

PURPOSE: To identify and describe experiences of patients with colorectal cancer (CRC) who have neurotoxic side effects early in the oxaliplatin treatment period, and how neurotoxicity affects their daily lives. PARTICIPANTS & SETTING: 10 patients with stage II-III CRC were included. All were treated with adjuvant oxaliplatin postoperatively and assessed neurotoxicity via a platform-independent mobile phone-based system. Patients were recruited from two hospitals in southern Sweden from November 2013 to August 2014. METHODOLOGIC APPROACH: Qualitative interview study conducted through open-ended, face-to-face, qualitative interviews. Thematic analysis was used. FINDINGS: A main theme was identified. IMPLICATIONS FOR NURSING: Nurses have an obligation to communicate the importance of early detection of neurotoxicity. Mobile phone technology seems to be a valuable tool for monitoring patient-reported neurotoxicity to improve communication and supportive care.

The trajectory of neurotoxic side effects' impact on daily life: a qualitative study.

PURPOSE: The purpose of this study was to explore the experiences of oxaliplatin-induced neurotoxic side effects among patients with colorectal cancer (CRC) and how these side effects influenced their daily lives over time. METHODS: To assess neurotoxic side effects, ten patients were repeatedly interviewed. The patients were recruited from two hospitals in south of Sweden, had stage II-III CRC, and had been treated with adjuvant oxaliplatin postoperatively, from November 2013 to October 2015. They had received FOLFOX and XELOX, with a mean total dose of 791 mg oxaliplatin. After completed chemotherapy, at 3, 6, and 12 months into the post-treatment phase, 25 interviews were conducted and thematic analysis was used according to Braun and Clarke. RESULTS: Oxaliplatin-induced neurotoxicity affects patients in several ways in the long term. Four themes were identified: Expectation of cure, Dubiety, Normalization, and Learn to live with neurotoxicity. The findings of this study describe the trajectory of neurotoxicity and its impact on these patients' life situation. The findings confirmed that neurotoxicity is multi-faceted and that the experience of it changes over time. CONCLUSION: The desire to survive stimulates adaptations and strategies to manage daily life, and patients learn to live with the neurotoxic side effects. This study provides evidence that these patients need individual attention and support during the trajectory of neurotoxic side effects. Current care provision is inadequate due to a lack of knowledge of the ways in which neurotoxicity impacts the patient's daily life. This study provides insights that could be used to develop a more person-centered care.

Causes of death after surgery for colon cancer-impact of other diseases, urgent admittance, and gender.

OBJECTIVE. In patients with colon cancer, high age and comorbidity is common. In this population-based retrospective study we have investigated causes of death and the influence of urgent operation, and gender on survival. MATERIAL AND METHODS. Medical records of 413 patients with verified colon cancer were reviewed. The diagnosis was made during 2000-2006 and operation was performed in 385 patients (93%). RESULTS. The overall 5-year survival after surgery was 48.3%. At the end of the follow-up, 128 patients (54.9%) had verified colon cancer when they died but 105 patients (45.1%) had no signs of colon cancer. Their 5-year survival was 5.5% and 41.9%, respectively (p < 0.0001). Median survival time was significantly shorter after urgent compared with elective admittance, 20.7 months versus 77.9 months, and the 5-year survival 32.4% versus 57.9% (p = 0.0001). The tumor stage at operation was more favorable in patients dying with no signs of colon cancer than in those dying with cancer regarding stage I-II (66.7% versus 16.4%), and stage IV (1.0% versus 53.1%), but not regarding stage III (30.5% versus 29.7%). The overall survival in women who were operated was longer than in men (p = 0.045) as well as survival after elective admittance (p = 0.013). CONCLUSION. After a median follow-up of 56.1 months almost half of the patients who were dead had died from other causes than colon cancer. Ten percent of those patients had an incorrectly reported diagnosis of colon cancer as cause of death. Urgent admittance was associated with reduced survival time. The median survival time was longer in women than in men.

Common Symptoms and Distress Experienced Among Patients with Colorectal Cancer: A Qualitative part of Mixed Method Design.

BACKGROUND: Colorectal cancer is one of the most common types of tumour in the world. Treatment side effects, together with the tumour symptoms, can result in a 'symptom burden'. To understand the patient's burden during chemotherapy treatment and plan effective symptom relief there is a need for more knowledge about the experience of symptoms from the patients' perspective. OBJECTIVES: The study was designed to qualitatively identify and describe the most common symptoms among patients treated for colorectal cancer, and discover whether there are barriers to reporting symptoms. METHODS: Thirteen Swedish patients diagnosed with colorectal cancer and treated with chemotherapy were interviewed face-to-face. The interviews were audio-taped and transcribed verbatim. The transcripts were analysed by following the principles of qualitative content analysis. RESULTS: Nine symptoms/forms of distress were identified. Those most frequently expressed were fatigue, changed bowel habits, and affected mental well-being, closely followed by nausea, loss of appetite and neurological problems. Of particular note were the affected mental well-being, the magnitude of the neurological problems described, the symptoms related to skin and mucous membrane problems, and the reports of distressing pain. Barriers to symptom control were only expressed by the patients in passing and very vaguely. CONCLUSION: This study confirms other reports on most common symptoms in colorectal cancer. It also highlights the early onset of symptoms and provides data on less well-studied issues that warrant further study, namely affected mental well-being, the magnitude of the neurological problems and symptoms related to the skin and mucous membranes. Nurses need to be sensitive to the patients' need presented and not only noting symptoms/distresses they have guidelines for.

Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study.

PURPOSE: The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. PATIENTS AND METHODS: Patients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points. RESULTS: Of the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. CONCLUSION: Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.

Impact of PINCH expression on survival in colorectal cancer patients.

BACKGROUND: The adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer. In this study we further investigate the relationship of PINCH and survival regarding the response to chemotherapy in colorectal cancer. RESULTS: Paraffin-embedded tissue sections from 251 primary adenocarcinomas, 149 samples of adjacent normal mucosa, 57 samples of distant normal mucosa and 75 lymph node metastases were used for immunohistochemical staining. Stromal staining for PINCH increased from normal mucosa to primary tumour to metastasis. Strong staining in adjacent normal mucosa was related to worse survival independently of sex, age, tumour location, differentiation and stage (p = 0.044, HR, 1.60, 95% CI, 1.01-2.52). PINCH staining at the invasive margin tended to be related to survival (p = 0.051). In poorly differentiated tumours PINCH staining at the invasive margin was related to survival independently of sex, age and stage (p = 0.013, HR, 1.90, 95% CI, 1.14-3.16), while in better differentiated tumours it was not. In patients with weak staining, adjuvant chemotherapy was related to survival (p = 0.010, 0.013 and 0.013 in entire tumour area, invasive margin and inner tumour area, respectively), but not in patients with strong staining. However, in the multivariate analysis no such relationship was seen. CONCLUSIONS: PINCH staining in normal adjacent mucosa was related to survival. Further, PINCH staining at the tumour invasive margin was related to survival in poorly differentiated tumours but not in better differentiated tumours, indicating that the impact of PINCH on prognosis was dependent on differentiation status.

Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group.

Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.

Aspects on priority settings in cancer treatment and care.

The widening gap between available resources and increasing possibilities to diagnose and treat different medical conditions has resulted in new attention to priority setting. The issue is complicated and harbours several obstacles because of different valuations concerning the needs of patient groups, the true results (patient benefit) of medical actions, and also important ethical considerations. Earlier attempts have been unsuccessful in introducing a prioritization milieu into the medical profession, probably due to vague requests for an open and sharp prioritization process. With a sharpened competition of allocating resources for different medical actions, the medical profession of the cancer sector needs to have a tool for explaining consequences for the different cancer patient groups and what is achieved by the cancer treatments and the care. A model for ranking lists consisting of pairs of patient conditions and medical actions is presented, and the principle for using these lists for priority setting in medical society is discussed.

Concentrations of polychlorinated biphenyls in blood and the risk for testicular cancer.

An increasing incidence of testicular cancer has been reported from several western countries during the last decades. According to current hypothesis testicular cancer is initiated during the foetal period and exposure to endocrine disruptors such as some persistent organic pollutants has been of concern. We have previously reported the results for concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB) and chlordanes in 58 cases with testicular cancer, 61 age-matched controls and 44 case mothers and 45 control mothers. In that report, significant increase of odds ratio (OR) was found for sum of PCBs, HCB, trans- and cis-nonachlordane in case mothers. These data have now been further analysed for 37 congeners of PCBs. No significant differences were found among cases and controls. However, case mothers had significantly increased concentrations of a number of PCB congeners. A priori decided grouping of PCBs yielded for oestrogenic PCBs OR = 2.4, 95% confidence interval (CI) = 0.95-6.0, enzyme-inducing PCBsOR = 2.6, 95% CI = 1.03-6.5 and toxic equivalents (TEQ) yielded OR = 3.3, 95% CI = 1.3-8.4. These data further elucidate the role of foetal exposure to different PCB congeners in the aetiology of testicular cancer.

Urinary excretion of 8-hydroxydeoxyguanosine and malondialdehyde after high dose radiochemotherapy preceding stem cell transplantation.

The urinary excretion of the hydroxylated DNA base 8-hydroxydeoxyguanosine (8-OHdG) and the lipid peroxidation product malondialdehyde (MDA) was monitored in 11 patients with hematological malignancies undergoing total body irradiation and high-dose chemotherapy preceding bone marrow transplantation. Nine patients showed a prompt increase in urinary 8-OHdG (8-25 times the initial baseline level) on days 0-7 after irradiation onset; the excretion then decreased during the aplastic period and increased again when engraftment took place (in 7 patients). A significant positive correlation was found between urinary 8-OHdG and whole blood leukocyte count, both on day 5 (p =.04, r =.72) and on day 22 (p =.009, r =.80) after irradiation onset. One patient who lacked the first peak of 8-OHdG excretion showed low blood leukocyte counts (less than 2 x 10(9)/l) before therapy onset; this patient, however, later had a successful engraftment and then also showed considerable increases in both 8-OHdG excretion and leukocyte count. These observations suggest leukocytes play a part in the excretion of 8-OHdG after conditioning therapy preceding bone marrow transplantation. As opposed to the biphasic 8-OHdG excretion, the excretion of MDA showed a single peak appearing on days 11-19 after radiochemotherapy onset, i.e., during the period in which the patients suffered from cytopenia, mucositis, and other side effects of the treatment. It is suggested, therefore, that these clinical manifestations are associated with increased lipid peroxidation. Altogether, these findings illustrate the utility of serial urinary samples for monitoring oxidative stress due to conditioning therapy in clinical practice. They also demonstrate that different oxidative stress markers may behave quite differently regarding their appearance in the urine after whole-body oxidative stress.

Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer.

An increasing incidence of testicular cancer has been reported from several countries in the Western world during the last decades. According to current hypothesis, testicular cancer is initiated during the fetal period, and exposure to endocrine disruptors, i.e., xenoestrogens, has been of concern. In this investigation we studied the concentrations of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched controls. Furthermore, case and control mothers were also asked to participate, and 44 case mothers and 45 control mothers agreed. They were of similar age. In cases only the concentration on lipid basis of cis-nonachlordane was significantly increased, whereas case mothers showed significantly increased concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio (OR) of 3.8; 95% confidence interval (CI), 1.4-10 was calculated using the median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 (95% CI, 1.7-12); for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11); for cis-nonachlordane, OR = 3.1 (95% CI, 1.2-7.8); and for sum of chlordanes, OR = 1.9 (95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma or nonseminoma testicular cancer.

Chemotherapy of soft tissue sarcoma--a clinical evaluation of treatment over ten years.

The aim of the study was to evaluate the effect of palliative chemotherapy on soft tissue sarcomas given outside controlled trials. Therapy and response rates of 77 patients with non-resectable sarcoma treated with different regimens between 1991 and 2000 were reviewed. Thirty-six patients were treated with first-line chemotherapy comprising cyclophosphamide+vincristine+doxorubicin+dacarbazine (CYVADIC), with a response rate of 28% (median response duration 5.5 months). Etoposide and ifosfamide (IVP, or VIG, which also includes granulocyte colony-stimulating factor (G-CSF)) were used in the treatment of 18 patients. The response rate was 22% (median response duration 4.5 months); Nineteen patients were treated with doxorubicin+ifosfamide and one patient responded. Four patients received other first-line treatments. Thirty-eight patients were given second-line chemotherapy and 4 (10%) patients responded. Thirteen patients were given third-line treatment and 5 patients received fourth-line treatment, but without any response. Disease progression was the dominant reason for discontinuation of therapy. The response rate in the present study was lower than the best published results, probably due to the fact that our soft tissue sarcoma patient material was unselected. Treatment with CYVADIC yields at least as high a response rate as the more recently described doxorubicin+ifosfamide combination, but third- and fourth-line therapy is not beneficial. Clinical trials with more active drugs are needed, as are more predictive and prognostic tests and a better selection of patient groups suited for different treatment options for soft tissue sarcomas.

Patterns of referral to a palliative care unit: an indicator of different attitudes toward the dying patient?

In 1996 a specialized palliative care unit was opened at the Linköping University Hospital in Sweden and different patterns of referral from different parts of the district soon became apparent. The aim of this study was to investigate the mechanisms underlying these patterns. During the first 6 months, 133 referrals were analyzed. The stated reason for referral and the actual content of care were, in each case, classified into five groups: symptom control, terminal care, rehabilitation, respite care, and special treatment and investigations. The stated reason for referral and the content of care coincided in three groups: terminal care, rehabilitation, and special treatment and investigations. When symptom control was the stated reason for referral, it was the main content of care in only 33 of 78 cases, while terminal care was the actual main content in 28 of 78 cases. Variations in patterns of referral were also observed in the different hospital-based home care teams (HBHC). In our study differences in the three HBHC teams regarding knowledge, skill, and attitudes might be reflected in variations in patterns of referral. The results illustrate the need for further education regarding referral indications, improvements in documentation of reason for referral, improved communication between HBHC teams and the palliative care unit, and improved prognostication at the end of life.