Far-advanced Cancer Research Articles

Factors related to accurate clinicians' prediction of survival: an international multicenter study in East Asia.

Recent guidelines for prognostic evaluation recommend clinicians' prediction of survival (CPS) for survival prediction in patients with advanced cancer. However, CPS is often inaccurate and optimistic. Studies on factors associated with overestimation or underestimation of CPS are limited. We aimed to investigate the factors associated with the overestimation and underestimation of CPS in patients with far-advanced cancer. The current study was a secondary analysis of an international multicenter prospective cohort study, which enrolled newly admitted patients with advanced cancer in palliative care units (PCUs) in Japan, Korea, and Taiwan from 2017 to 2018. We obtained the temporal CPS at enrollment and performed multivariate logistic regression analysis to identify the factors associated with "underestimation (less than 33% of actual survival)" and "overestimation (more than 33% of actual survival)." A total of 2571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. Older age (adjusted odds ratio [aOR] 1.01; 95% confidence interval [CI] 1.01-1.02; P < 0.01) and reduced oral intake (aOR 0.68; 95% CI 0.51-0.89; P < 0.01) were identified as significant factors associated with underestimation. Dyspnea (aOR 1.28; 95% CI 1.06-1.54; P = 0.01) and hyperactive delirium (aOR 1.34; 95% CI 1.05-1.72; P = 0.02) were identified as significant factors associated with overestimation. Older age was related to underestimation, while dyspnea and hyperactive delirium were related to overestimation of CPS for patients with weeks of survival. However, reduced oral intake was less likely to lead to underestimation.

How different are accuracies of clinicians' prediction of survival by assessment methods?

No standardized method has been established for evaluating the accuracy of a clinicians' prediction of survival (CPS). Till now, no study has compared the accuracy of CPS according to the evaluation methods using the same dataset. We aimed to examine the accuracy of CPS by different statistical approaches in patients with far-advanced cancer. The current study was a secondary analysis of an international multicenter prospective cohort study. Newly admitted patients with advanced cancer were enrolled in palliative care units (PCUs) in Japan, Korea, and Taiwan. We obtained the temporal CPS at enrollment. The patients were classified into groups of days (≤7 days) and weeks (≤30 days) based on CPS and actual survival (AS). We evaluated the accuracy of CPS by the distribution, area under the receiver operating characteristics curve (AUROCs), and an estimate ±33% of AS. A total of 2,571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. As for the "days" category, the distribution of AS is larger than that of CPS, however, the results are reversed in the "weeks" category. The AUROCs showed over 80% discrimination for both the "days" and "weeks" categories. Accurate CPS within ±33% of AS was approximately 30% in both "days" and "weeks" categories. We showed a discrepancy of approximately 30-80% in the accuracy of CPS among three different analysis methods: distribution, AUROC, and AS comparison. Considering the low accuracy of AS comparisons, clinicians should provide a wide range of survival time. CPS was able to effectively discriminate and may be useful for risk stratification.

Management of venous thromboembolism in far-advanced cancer: current practice

ObjectivesVenous thromboembolism (VTE) is common in advanced cancer. Guidelines suggest that indefinite anticoagulation be considered for patients with ongoing active cancer. There are no data on the management of cancer-associated...

Botulinum Toxin Injection for Intractable Pain in Cancer Patients With Psoas Muscle Invasion

Muscle invasion (MI) in patients with far-advanced cancer is often accompanied with pain. Conventional treatments used for pain relief may be associated with several side effects.We describe two cases of botulinum toxin injection (BTI) for relieving intractable pain in patients of far-advanced cancer having MI. The patients presented with persistent intractable pain that did not respond to conventional treatments, such as analgesic medications, epidural steroid injection, and radiotherapy. BTI relieved the intractable pain in these cases for at least 9–12 weeks without any reported side effects. We suggest that BTI can be an alternative method to relieve intractable pain associated with MI in patients with far-advanced cancer.

Comparison of the accuracy of clinicians' prediction of survival and Palliative Prognostic Score: an East Asian cross-cultural study.

No study has been conducted to compare the clinicians' prediction of survival (CPS) with Palliative Prognostic Scores (PaP) across countries. We aimed to compare the performance of the CPS in PaP (PaP-CPS), the PaP without the CPS, and the PaP total scores in patients with advanced cancer in three East Asian countries. We compared the discriminative accuracy of the three predictive models (the PaP-CPS [the score of the categorical CPS of PaP], the PaP without the CPS [sum of the scores of only the objective variables of PaP], and the PaP total score) in patients admitted to palliative care units (PCUs) in Japan, Korea, and Taiwan. We calculated the area under the receiver operating characteristic curve (AUROC) for 30-day survival to compare the discriminative accuracy of these three models. We analyzed 2,072 patients from three countries. The AUROC for the PaP total scores was 0.84 in patients in Japan, 0.76 in Korea, and 0.79 in Taiwan. The AUROC of the PaP-CPS was 0.82 in patients in Japan, 0.75 in Korea, and 0.78 in Taiwan. The AUROC of the PaP without the CPS was 0.75 in patients in Japan, 0.66 in Korea, and 0.67 in Taiwan. The PaP total scores and the PaP-CPS consistently showed similar discriminative accuracy in predicting 30-day survival in patients admitted to PCUs in Japan, Korea, and Taiwan. It may be sufficient for experienced clinicians to use the CPS alone for estimating the short-term survival (less than one month) of patients with far-advanced cancer. The PaP may help to improve prognostic confidence and further reduce subjective variations.

Comparison of Objective Prognostic Score and Palliative Prognostic Score performance in inpatients with advanced cancer in Japan and Korea.

Accurate prognostication is important for patients and their families to prepare for the end of life. Objective Prognostic Score (OPS) is an easy-to-use tool that does not require the clinicians' prediction of survival (CPS), whereas Palliative Prognostic Score (PaP) needs CPS. Thus, inexperienced clinicians may hesitate to use PaP. We aimed to evaluate the accuracy of OPS compared with PaP in inpatients in palliative care units (PCUs) in three East Asian countries. This study was a secondary analysis of a cross-cultural, multicenter cohort study. We enrolled inpatients with far-advanced cancer in PCUs in Japan, Korea, and Taiwan from 2017 to 2018. We calculated the area under the receiver operating characteristics (AUROC) curve to compare the accuracy of OPS and PaP. A total of 1,628 inpatients in 33 PCUs in Japan and Korea were analyzed. OPS and PaP were calculated in 71.7% of the Japanese patients and 80.0% of the Korean patients. In Taiwan, PaP was calculated for 81.6% of the patients. The AUROC for 3-week survival was 0.74 for OPS in Japan, 0.68 for OPS in Korea, 0.80 for PaP in Japan, and 0.73 for PaP in Korea. The AUROC for 30-day survival was 0.70 for OPS in Japan, 0.71 for OPS in Korea, 0.79 for PaP in Japan, and 0.74 for PaP in Korea. Both OPS and PaP showed good performance in Japan and Korea. Compared with PaP, OPS could be more useful for inexperienced physicians who hesitate to estimate CPS.

Implantation of permanent pleural catheter for palliation of malignant pleural effusion.

PurposeMalignant pleural effusion (MPE) is a disabling condition caused in most instances by far-advanced cancer. The treatment is palliative and should ideally be minimally invasive. The aim of this retrospective study was to evaluate the effectiveness of implantation of a permanent PleurX catheter in the treatment of recurrent MPE in patients with terminal cancer disease.Patients and methodsEighteen consecutive patients with terminal cancer and MPE, who had a permanent PleurX catheter implanted in the period from February 2014 to August 2015, were retrospectively evaluated. Medical records were reviewed for data on procedures and patients.ResultsTwenty-two PleurX catheters were implanted in the pleural cavity of 18 patients. The technical success rate was 100%. All patients had relief of symptoms. Catheter patency was 91%. Six patients experienced minor adverse events (AEs) and two patients experienced moderate-to-severe AEs. The median survival time for the 14 patients who died during follow-up was 45 days.ConclusionImplantation of a permanent PleurX catheter is a safe procedure with a high success rate and only few AEs. The procedure has the potential to serve as an effective procedure for palliation of recurrent MPE in terminal cancer patients.

Prospective Validation of the Objective Prognostic Score for Advanced Cancer Patients in Diverse Palliative Settings

ContextPrognostication is an essential part of palliative care to aid decision making and negotiate goals of care. The Objective Prognostic Score (OPS) is an easy-to-use prognosticating tool to predict survival among far-advanced cancer patients in palliative care units (PCUs) in Korea. ObjectivesThis study aimed to prospectively validate the OPS for advanced cancer patients in the palliative care teams (PCTs), PCUs, and home-based palliative care (HPC) in Japan. MethodsThis was a substudy of a multicenter prospective cohort study that was conducted to validate and compare prognostic tools among advanced cancer patients in Japan. Participants' survival was calculated according to OPS 3 as a cutoff for predicting survival of less than three weeks. Overall accuracy and area under the receiver operator characteristic curves of OPS 3 were calculated for PCT, PCU, and HPC, respectively. ResultsA total of 1146 cases (PCTs 441, PCUs 519, and HPCs 186 cases) were included in final analyses. The overall accuracy of OPS 3 for predicting three-week survival ranged from 0.70 to 0.78 across diverse palliative care settings. The c-statistics ranged from 0.742 to 0.808 across three settings. Participants in the PCT showed the highest overall accuracy and c-statistics for OPS. ConclusionThe OPS can be used for prognostication among advanced cancer patients in PCT, PCU, and HPC settings.

腹部大動脈瘤に対するステントグラフト内挿術の費用対効用分析

Objective: To assess medical economic adequacy of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). Methods: Cost-utility analysis. A total of 21 patients with AAA treated at Ibaraki Prefectural Central Hospital in 2014 were divided into non-ruptured EVAR (Group E) and open surgery (OS) (Group O), and ruptured OS (Group R) groups, and hospital costs were aggregated with a medical accounting system. Mid-level hospital costs were estimated by a diagnosis-procedure-combination analysis system. Incremental life years were extrapolated from the results of randomized controlled trials in the UK (EVAR Trial 1 and 2), a life table, and the Pancreas Cancer Registry in Japan. Quality-adjusted life years (QALY) were estimated under the assumption of a certain quality weight. Results: Incremental cost-effectiveness ratio (ICER) of EVAR compared with the OS was calculated to be 31.0 million yen/QALY, which is economically inadequate. ICER of EVAR compared with conservative treatment was inadequate in some subgroups of extremely old patients and in patients operated for far-advanced cancer. Conclusion: EVAR is inadequate with respect to medical economics as a substitute for OS for patients in whom both procedures are available. The indication for EVAR in patients ineligible for OS should be different from that for surgery in usual patients with AAA. (This is a translation of J Jpn Coll Angiol 2016; 56: 123-130.).

If Not Us, Then Who?

“If not you, then who?” These words were spoken to me by a wise and deeply concerned mentor during a time of extreme doubt that I was experiencing as a medical intern. I was wondering whether I had anything of value at all to offer the patients under my care who were dying from far-advanced cancer. This simple but profound rhetorical rejoinder to my expressed sense of inadequacy turned me on my heel, actually and metaphorically, to return and attend to my patients as they lay dying, with conviction no longer to be demoralized by the absence of my ability to prescribe a cure but rather to be motivated to help reduce the burden imposed by their disease. Several years later, and seemingly a world apart from that linoleum-lined county hospital, I was sitting in an oak and gilded board room of a prestigious cancer center at a meeting to discuss cancer care. Upper echelon directors of the center were proudly reviewing the latest data demonstrating small but notable increases in 5-year survival rates for patients treated there with certain solid tumors. Ebullience and …

Living with Advanced Cancer and Short Life Expectancy: Patients’ Experiences with Managing Medication

Our aim is to explore patients' experiences of using medicines when they are living with far-advanced cancer and short life expectancy; our method is a qualitative interview study. At a daycare centre at a palliative clinic in Norway, we interviewed 15 patients with advanced incurable cancer with multiple metastases who had a short life expectancy. We found that in taking their medications, they feared losing control, becoming addicted, or suffering harmful effects. Non-compliance was the rule, not the exception: patients juggled doses or dosage intervals, or they stopped taking the medications. They wanted to take as little medication as possible and self-manage it to gain control over their lives. We concluded that patients need to discuss their medication practice. If they choose alternative medication strategies, that choice must be respected. For patients, the issue is self-management, not compliance. Patients with a short life expectancy want to negotiate their medication practice with health care professionals and take an active role in tailoring it to suit their preferences. Health professionals should therefore consider a concordance rather than a compliance model for these patients.

Recent Advances in the Diagnosis and Management of Malignant Pleural Effusions

Malignant pleural effusions (MPEs) are an important complication for patients with intrathoracic and extrathoracic malignancies. Median survival after diagnosis of an MPE is 4 months. Patients can present with an MPE as a complication of far-advanced cancer or as the initial manifestation of an underlying malignancy. Common cancer types causing MPEs include lymphomas, mesotheliomas, and carcinomas of the breast, lung, gastrointestinal tract, and ovaries. However, almost all tumor types have been reported to cause MPEs. New imaging modalities assist the evaluation of patients with a suspected MPE; however, positive cytologic or tissue confirmation of malignant cells is necessary to establish a diagnosis. Even in the presence of known malignancy, up to 50% of pleural effusions are benign, underscoring the importance of a firm diagnosis to guide therapy. Rapidly evolving interventional and histopathologic techniques have improved the diagnostic yield of standard cytology and biopsy. Management of an MPE remains palliative; it is critical that the appropriate management approach is chosen on the basis of available expertise and the patient's clinical status. This review summarizes the pathogenesis, diagnosis, and management of MPE. Studies in the English language were identified by searching the MEDLINE database (1980-2007) using the search terms pleura, pleural, malignant, pleurodesis, and thoracoscopy.

Treatment of Nausea and Vomiting in Terminally Ill Cancer Patients

Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.

Serum Interleukin-12 Levels in Patients with Gastric Cancer

To evaluate the immunological status of patients with gastric cancer before surgery, we investigated the relationship between serum interleukin-12 (IL-12) levels and clinicopathological factors. We measured serum IL-12 levels in 127 patients with gastric cancer and 35 healthy controls, by a sandwich enzyme-linked immunosorbent assay using the Human IL-12 +p40 Immunoassay kit. The serum IL-12 levels in the patients with gastric cancer were significantly higher than those of the healthy controls (P < 0.05). There were no significant differences in disease stage or gross appearance among the cancer groups, but the serum IL-12 levels in patients with T4 disease were significantly lower than those in patients with T1, T2, or T3 (P < 0.01). There were no significant differences in serum IL-12 levels between patients with and those without lymph node, liver, or peritoneal metastasis. The serum IL-12 levels in patients with distant metastasis were significantly lower than those in patients without distant metastasis (P < 0.02). There were no significant differences in the serum IL-12 levels according to classification by histopathological findings. Analysis with the linear correlation coefficient showed no significant correlation between serum IL-12 and serum carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, CA 72-4, alpha-fetoprotein, or immunosuppressive acidic protein. However, there was a significant relationship between serum IL-12 levels and soluble IL-2 receptor levels (r = 0.53, P < 0.01). Serum IL-12 levels in patients with far-advanced gastric cancer were significantly lower than those in patients with less-advanced gastric cancer. This is because macrophages in patients with far-advanced cancer would be hectic and unable to produce sufficient IL-12.

Systematic review of the efficacy of antiemetics in the treatment of nausea in patients with far-advanced cancer.

To systematically review studies of antiemetics used in the treatment of nausea in patients with far-advanced cancer. Randomized controlled trials (RCT) and uncontrolled studies identified by electronic and hand searching. Identified studies were appraised for quality and effect size. Of 21 studies included, 2 were systematic reviews, 7 were RCT and 12 were uncontrolled studies or case series. Differences in interventions and outcomes amongst the RCT precluded any quantitative data synthesis and all seven studies were prone to bias. Whereas uncontrolled studies indicated a high response rate to standard regimens (75-93% for both nausea and vomiting), RCT showed much lower response rates to these agents (23-36% for nausea, 18-52% for vomiting). The two methods of antiemetic choice (choice based either on the inferred mechanism or empirical) were equally effective. There is reasonably strong evidence for the use of metoclopramide in cancer-associated dyspepsia and steroids in malignant bowel obstruction. There was conflicting evidence about the efficacy of serotonin antagonists compared with standard treatments (e.g. metoclopramide, dopamine antagonists and dexamethasone). There was little or no evidence of the efficacy of some commonly used and seemingly effective drugs such as haloperidol, cyclizine, and methotrimeprazine. Evidence supporting the existing consensus-based guidelines for management of nausea and vomiting in advanced cancer is sparse. Current approaches to treatment based on the neuropharmacology of the emetic pathway may be inappropriate in this setting. Well-designed studies of the impact of "standard" management and novel agents on nausea and vomiting in palliative populations are needed.

Spain: The WHO Demonstration Project of Palliative Care Implementation in Catalonia: Results at 10 Years (1991–2001)

Xavier Gomez-Batiste, MD, Josep Porta, PhD, MD, Albert Tuca, MD, Esther Corrales, RN, Federico Madrid, MD, Jordi Trelis, MD, Dulce Fontanals, SW, Josep M. Borras, PhD, MD, Jan Stjernsward, PhD, MD, Antoni Salva, MD, and Eduard Rius, MD Palliative Care Service (X.G.-B., J.P., A.T., E.C., F.M., J.T.), Institut Catala d’Oncologia, Barcelona, Spain; Fundacio SAR (D.F.), Barcelona, Spain; Institut Catala d’Oncologia (J.M.B), Barcelona, Spain; Global Cancer Concern (J.S.), Stockholm, Sweden; Divisio Sociosanitaria (A.S.), Servei Catala de la Salut, Barcelona, Spain; and Ministry of Health (E.R.), Government of Catalonia, Barcelona, Spain

Low-Dose Ketamine in the Management of Opioid Nonresponsive Terminal Cancer Pain

Two patients with far-advanced cancer, near death, who were experiencing excruciating and intractable pain that was poorly responsive to rapidly escalating doses of morphine and hydromorphone were treated with low-dose intravenous ketamine (0.1–0.2 mg/kg). This intervention eliminated the need for any further opioid use, providing profound analgesia and a sense of calm during the last hours and days of these patients’ lives. These case reports add to the small but growing body of clinical literature suggesting that ketamine may have a significant place in the care of patients with pain that is poorly responsive to opioids, or who experience dose-limiting adverse effects, near the end of life. This is an important matter to disseminate in order to reassure the public that we do have the tools necessary to keep the promise that no one need die with uncontrolled pain. This therapeutic approach may also serve to reassure concerned physicians that their efforts to assure pain relief may not be misconstrued as hastening death.

Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial

The aim of this study was to evaluate a low-dose regimen of megestrol acetate (MA; 320 mg/day) on appetite in advanced cancer patients. Out-patients with far-advanced non-hormone responsive tumours and loss of appetite were randomised in a phase III trial, with two consecutive phases: a 14-day double-blind placebo controlled phase (phase A) and a 76-day open phase (phase B). During phase A, patients were treated with MA, two 160 mg tablets/day, or placebo. In phase B, the MA dose was titrated to clinical response in both groups. Appetite, food intake, body weight, performance status, mood and quality of life were evaluated with standardised measures; patients’ global judgement about treatment efficacy was also requested. Of 42 patients entering the study, 33 (17 MA and 16 placebo) were evaluable for efficacy. The appetite score improved significantly with MA after 7 days ( P=0.0023), and this effect was still significant at 14 days ( P=0.0064). Patients judged the treatment with MA effective in 88.2% of cases (14th day), whilst placebo was considered effective by 25% ( P=0.0003). None of the other measures showed significant changes during treatment. The remarkable effect on appetite evident after 7 days, without serious side-effects, shows that MA can produce significant subjective effects at a low-dose even in patients with far-advanced disease.

Tropisetron versus Metoclopramide in the Control of Emesis in Far-Advanced Cancer

The present study was conducted to assess the optimum treatment for nausea and vomiting in patients with far advanced cancer. More specifically, we studied patients with cancers that were too far advanced to benefit from chemotherapy or radiotherapy and whose nausea and vomiting were not due to drug intake, cranial, electrolytic, or metabolic causes. One hundred twenty patients who were under antiemetic medication with metoclopramide (MET) and suddenly presented with uncontrolled nausea and vomiting were randomized to three different therapeutic regimens: MET plus dexamethasone (DEX), MET plus tropisetron (TRO), and MET plus TRO plus DEX. Patient diary cards were used to assess nausea and vomiting. By the end of day 15, total control of vomiting was achieved in 24% of MET plus DEX patients, in 84% of MET plus TRO patients, and in 92% of MET plus TRO plus DEX patients. Total control of nausea was achieved in 18% of MET plus DEX patients, in 74% of MET plus TRO patients, and in 87% of MET plus TRO plus DEX patients. All antiemetic treatments were similarly well tolerated. TRO in combination with either MET or MET and DEX produced the best control of both nausea and vomiting.

Cisplatin, 5-Fluorouracil, and High-Dose Folinic Acid in Patients with Advanced Unresectable Head and Neck Cancer

For patients with advanced, unresectable head and neck (HN) cancer, surgery and/or radiotherapy are the standard treatments but have poor results. A phase II trial of a continuous infusion of cisplatin, 5-FU, and high dose folinic acid (PFL) as induction chemotherapy in patients with previously untreated, locally advanced HN cancer was performed in an attempt to confirm the encouraging results reported by Dana Farber investigators using an identical regimen. Forty-five consecutive patients with unresectable HN cancer were treated every 28 days with a continuous infusion of cisplatin 25 mg/m(2)/day (days 1-5), 5-FU 800 mg/m(2)/day (days 2-6), and folinic acid 500 mg/m(2)/day (days 1-6). After three courses of chemotherapy, patients were treated with surgery and/or radiotherapy. Objective responses were observed in 26 of 38(69%) evaluable patients with 14(37%) clinical complete responses. Grade III-IV toxicity was important and consisted mainly of mucositis and neutropenia that were found in 47 and 18%, respectively , of patients after the first course. There was one toxic death. PFL is an active, toxic induction regimen for far-advanced HN cancer, yielding a response rate in the range of the widely used cisplatin and 5-FU (PF) schedule; a comparative trial is warranted before concluding that PFL is superior to the latter combination.