The orthomolecular treatment of cancer. I. The role of ascorbic acid in host resistance

Natural resistance to neoplastic disease governs the incidence of clinical cancer and influences the individual's response to standard methods of treatment. Supportive measures, specifically designed to enhance the natural resistance of the host, should diminish cancer incidence, morbidity and mortality. The various factors involved in host resistance are briefly reviewed, and it is contended that the availability of ascorbic acid plays an important role in many of these physiological processes. The potential value of ascorbic acid in the supportive treatment of cancer is a matter for urgent study at many levels. It offers the promise of general improvement in the results of cancer management, including prophylaxis in general, supportive therapy when standard methods of treatment are being used, and palliative treatment in advanced terminal cancer.     

Music therapy in supportive cancer care

The purpose of this paper is to show some aspects of music therapy application in cancer care and to present the integration of music therapy program into a continuous supportive cancer care for inpatients. A cancer diagnosis is one of the most feared and serious life events that causes stress in individuals and families. Cancer disrupts social, physical and emotional well-being and results in a range of emotions, including anger, fear, sadness, guilt, embarrassment and shame. Music therapy is a part of a complementary medicine program in supportive cancer care which accompanies medical treatment. There are many benefits of music therapy for cancer patients—interactive music therapy techniques (instrumental improvisation, singing) as well as receptive music therapy techniques (listening to recorded or live music, music and imaginary) can be used to improve mood, decrease stress, pain, anxiety level and enhance relaxation. Music therapy is an effective form of supporting cancer care for patients during the treatment process. It may be also basic for planning effective programs of rehabilitation to promote wellness, improve physical and emotional well-being and the quality of life.     

Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.

OBJECTIVES--To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care. DESIGN--Randomised study. SETTING--Gastrointestinal oncology departments. PATIENTS--40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic. INTERVENTIONS--Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle. MAIN OUTCOME MEASURES--Length of survival and quality of life score with an optimised functional living index-cancer scale. RESULTS--Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm. CONCLUSIONS--In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.     

Factors affecting survival after palliative radiotherapy in patients with lung cancer

BackgroundLung cancer is the most common cancer worldwide. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to identify factors that play a major role in the survival of lung cancer patients treated with palliative radiotherapy.Materials and methodsWe retrospectively reviewed data of 280 lung cancer patients treated with palliative radiotherapy from January 2013 to December 2017. A multivariate analysis using the proportional hazards model of Cox was conducted. Also, Kaplan Meier curves were used to describe the distribution of survival times of the patients. The level of significance was set at 0.05.ResultsThe mean age at diagnosis was 65.6 years. About 77.5% of patients were male and 22.5% were female. In our cohort > 95% had stage 4 lung cancer. Most cases were adenocarcinomas (72.5%) and ECOG-PS 0–1 (80.4%). Different sites were submitted to palliative treatment: 120 brain metastases, 96 bone metastases, 53 lung tumour, 8 lymph nodes and 3 lung metastases. Brain as first site of palliative radiotherapy (HR: 1.553, 95% CI: 1.167–2.067, p = 0.003) and ECOG-PS 2–3 compared with ECOG-PS 0–1 (HR: 2.253, 95% CI: 1.546–3.283, p ≤ 0.001) were associated with increased likelihood of lung cancer death. Patients who received biological therapy had 70.7% (p ≤ 0.001) reduction in lung cancer death risk.ConclusionBrain as the first metastatic site treated with radiotherapy and ECOG-PS 2–3 are associated with increased lung cancer death. Biological therapy was associated with decreased death risk.     

Gemcitabine in the first and second-line chemotherapy of advanced non-small cell lung cancer

Aim of this study was to estimate efficacy of gemcitabine in first and the second-line chemotherapy for patients with advanced non-small cell lung cancer (stage III and IV). In first-line chemotherapy, 120 patients were treated with different chemotherapy regimens. Fifty-nine patients were treated with gemcitabine / cisplatin (PG), 41 with cisplatin / etoposide (PE) and 20 with mitomycin / ifosfamide / cisplatin (MIC). Forty patients, unsuccessfully treated with PE and MIC in first-line therapy were treated with PG (24 pts) and with best supportive care (BSC) (16 pts). In first-line therapy PG was superior to PE and MIC protocol (mean survival (MS) 10 vs. 7 vs. 8.5 months). Response rate (RR) for PG in first-line therapy was 46% and 21% in second-line. We showed also significantly better survival in patients treated with PG in second-line chemotherapy comparing to best supportive care (MS 9 vs. 5.5 months). Toxic side effects for combination PG was acceptable. This study confirmed that PG combination is safe and effective as first and second-line chemotherapy for patients with advanced non-small cell lung cancer.     

Erythropoietin is a novel therapeutic option in the treatment of anemia caused by small cell lung cancer

Anemia is very common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases the patient's quality of life. Erythropoietin therapy is accessible in Hungary for the treatment of chemotherapy-induced anemia in patients suffering from small cell lung cancer. In our case report we present the case of a 62-year-old female small cell lung cancer patient with severe anemia, treated by erythropoietin-beta. The erythropoietin treatment provided the possibility of effective chemo- and radiotherapy. The patient's quality of life greatly improved due to the lack of the symptoms of anemia. The adequate use of erythropoietin is of great help to the physician in the management of small cell lung cancer patients, by improving the quality of life.     

Complex assessment of late side effects affecting quality of life - the "Debrecen model"

As the outcome of childhood cancer improved substantially during the last 3 decades, the attitude of pediatric oncology has changed from "cure at any cost" to "cure at least cost". We investigated factors affecting quality of life in long-term survivors of childhood cancer in the in- and outpatient clinics of the Department of Pediatric Hematology-oncology, Institute of Pediatrics, Medical and Health Science Center, Debrecen. As a part of a comprehensive follow-up care program, we focused our attention on nephrotoxicity, osteoporosis and on cardiovascular morbidity. For long-term survivors of childhood cancer sensitive and cost-effective diagnostic algorithms were developed that can help in guiding secondary and tertiary prevention programs, in addition to assessing accurately the condition of patients. We found that anti-cancer treatments, including some of the supportive interventions, have adverse effects on glomerular (10%) and tubular functions (37%), impair the balance of bone resorption and formation (69%) and increase the frequency of cardiovascular risk factors (62%) in a significant proportion of patients. Our data confirm and extend the findings of other investigators and cooperative groups. In conclusion, we consider it important that the treatment plans of high-risk patients with cancer should be aimed at preserving the anticancer potential of therapy, without enhancing the frequency and severity of complications. The presented "Debrecen model" may help in achieving this goal and in increasing quality of life of long-term survivors of childhood cancer.     

Chemotherapy versus supportive care alone in pediatric palliative care for cancer: comparing the preferences of parents and health care professionals

Background:

The choice between palliative chemotherapy (defined as the use of cytotoxic medications delivered intravenously for the purpose of our study) and supportive care alone is one of the most difficult decisions in pediatric oncology, yet little is known about the preferences of parents and health care professionals. We compared the strength of these preferences by considering children’s quality of life and survival time as key attributes. In addition, we identified factors associated with the reported preferences.

Methods:

We included parents of children whose cancer had no reasonable chance of being cured and health care professionals in pediatric oncology as participants in our study. We administered separate interviews to parents and to health care professionals. Visual analogue scales were shown to respondents to illustrate the anticipated level of the child’s quality of life, the expected duration of survival and the probability of cure (shown only to health care professionals). Respondents were then asked which treatment option they would favour given these baseline attributes. In addition, respondents reported what factors might affect such a decision and ranked all factors identified in order of importance. The primary measure was the desirability score for supportive care alone relative to palliative chemotherapy, as obtained using the threshold technique.

Results:

A total of 77 parents and 128 health care professionals participated in our study. Important factors influencing the decision between therapeutic options were child quality-of-life and survival time among both parents and health care professionals. Hope was particularly important to parents. Parents significantly favoured chemotherapy (42/77, 54.5%) compared with health care professionals (20/128, 15.6%; p < 0.0001). The opinions of the physician and child significantly influenced the parents’ desire for supportive care; for health care professionals, the opinions of parents and children were significant factors influencing this decision.

Interpretation:

Compared with health care professionals, parents more strongly favour aggressive treatment in the palliative phase and rank hope as a more important factor for making decisions about treatment. Understanding the differences between parents and health care professionals in the relative desirability of supportive care alone may aid in communication and improve end-of-life care for children with cancer.Despite the substantial improvements in rates of cure among children with cancer, some children will have progressive or recurrent disease and will die.¹ Cancer remains the second most common cause of death for North American children between 5 and 14 years of age.^2–4 When cure becomes unlikely, parents and health care professionals are often faced with the decision to continue further aggressive treatments or to provide relief from symptoms alone.¹The choice between palliative chemotherapy and supportive care alone is one of the most important and difficult decisions for parents of children whose disease cannot be cured.⁵ At this point, the goals of therapy are usually to maximize the child’s quality and length of life and to ensure respect for the family’s and child’s preferences.⁶Given the difficult nature of this decision, it is worthwhile to compare and contrast the perspectives of parents and health care professionals. Discordance in these perspectives could heighten the anxiety felt by patients and parents and might lead to their dissatisfaction with the care received. One qualitative study that interviewed parents of children with recurrent cancer found that “fearing disagreement with staff” was an important negative factor in decision-making.⁷ However, little is known as to whether the attitudes of parents and health care professionals toward therapeutic options are congruent.The goal of this study was to compare the strength of preference between parents and health care professionals for supportive care alone versus palliative chemotherapy for children whose cancer has no reasonable chance of being cured, and to determine how specific factors affect these preferences.     

美国国家癌症研究所(National Cancer Institute)--美国癌症研究和资助的主要机构

美国国家癌症研究所(National Cancer Institute,NCI)成立于1937年,是国立卫生研究院(National Institutes of Health,NIH)历史最为悠久的研究所,也是美国癌症研究和资助的主要机构。通过立法及增加对癌症研究的投入,NCI在癌症研究领域取得一些成绩,使肺癌、结直肠癌、乳腺癌及前列腺癌的死亡率持续下降,另在胰腺癌、卵巢癌、白血病和甲状腺癌等肿瘤的诊断和治疗方面也取得了巨大成就。新近NCI制定了到20l5年的奋斗目标：“消除痛苦、减少死亡”,并将主要策略由“寻找进而破坏(seekanddestory)”转为“锁定并且控制(target and control)”。为了实现上述目标,NCI提出必须加强基础研究,以利癌症的早期发现(discovery);以此为基础,将实验室的研究结果尽快用于临床,促进各种治疗措施的发展(development);加强癌症防治的公共卫生宣传,以利于健康资讯的发布(delivery)。本文将简述NCI的历史沿革、主要目标、组织结构、资金预算以及所取得的成就。     

Radiotherapy in lung cancer. Mandatory or optional?

The purpose of the paper is to outline the current treatment strategies in lung cancer focusing on the possibile role of radiotherapy. METHOD: It defines the place of radiotherapy at the main histological types and stadiums proposing indications according to evidence based medicine. CONCLUSIONS: Radiotherapy is mandatory in non-operated NSCLC st. I-II in perioperative or palliative management of superior sulcus tumours; in the combined modality treatment of limited SCLC and in postoperative adjustment of resected single brain metastasis of lung cancer. It is optional after NSCLC segmentectomy; in palliation or postoperative adjuvation of NSCLC st. III Radiotherapy can be chosen as a part of best supportive care at NSCLC st. IV extensive SCLC and in case of multiple brain or localised lytic bone metastases.     

Osteonecrosis of the jaw developing during bisphosphonate treatment

The article discusses osteonecrosis of the jaw as a possible side effect of bisphosphonate treatment. It provides practical guidelines for prevention, diagnosis and management of bisphosphonate-associated osteonecrosis according to literature and clinical evidence. Since controlled clinical trials have not been carried out, the recommendations are based on reviews, reports and clinical experience. Osteonecrosis of the jaw (ONJ) is a historical clinical entity, which can potentially develop in cancer patients receiving bisphosphonate therapy. The pathogenesis of ONJ has not been totally revealed yet. A thorough dental/oral surgical examination and counseling is recommended in cases when intravenous bisphosphonate therapy is needed. All required dental and surgical treatment should be carried out before starting bisphosphonate therapy to prevent ONJ. The patient should be informed about the possible side effects, and the importance of good oral home care and regular dental check-ups. Once the intravenous bisphosphonate therapy has started, only conservative manipulations should be carried out in the oral cavity. Even in case of developed ONJ, suspension of bisphosphonate therapy is not necessary. In these cases a non-surgical approach is recommended concerning the treatment of ONJ. Regarding the growing number of ONJ cases in association with bisphosphonate therapy it is important for the professionals treating cancer patients to be aware of this phenomenon and the importance of prevention.     

Disruptions in sleep–wake cycles in community-dwelling cancer patients receiving palliative care and their correlates

Significant disruptions in sleep–wake cycles have been found in advanced cancer patients in prior research. However, much remains to be known about specific sleep–wake cycle variables that are impaired in patients with a significantly altered performance status. More studies are also needed to explore the extent to which disrupted sleep–wake cycles are related to physical and psychological symptoms, time to death, maladaptive sleep behaviors, quality of life and 24-h light exposure. This study conducted in palliative cancer patients was aimed at characterizing patients’ sleep–wake cycles using various circadian parameters (i.e. amplitude, acrophase, mesor, up-mesor, down-mesor, rhythmicity coefficient). It also aimed to compare rest–activity rhythm variables of participants with a performance status of 2 vs. 3 on the Eastern Cooperative Oncology Group scale (ECOG) and to evaluate the relationships of sleep–wake cycle parameters with several possible correlates. The sample was composed of 55 community-dwelling cancer patients receiving palliative care with an ECOG of 2 or 3. Circadian parameters were assessed using an actigraphic device for seven consecutive 24-h periods. A light recording and a daily pain diary were completed for the same period. A battery of self-report scales was also administered. A dampened circadian rhythm, a low mean activity level, an early mean time of peak activity during the day, a late starting time of activity during the morning and an early time of decline of activity during the evening were observed. In addition, a less rhythmic sleep–wake cycle was associated with a shorter time to death (from the first home visit) and with a lower 24-h light exposure. Sleep–wake cycles are markedly disrupted in palliative cancer patients, especially, near the end of life. Effective non-pharmacological interventions are needed to improve patients’ circadian rhythms, including perhaps bright light therapy.     

Complication of radiation therapy among patients with positive S. aureus culture from genital tract

AimThe main goal of this investigation was to evaluate the influence of positive Staphylococcus aureus culture from the genital tract on patients receiving radiation therapy, suffering from carcinoma of the uterus. The other aim was to observe radiation therapy complications.BackgroundRadiation therapy of patients suffering from cervical cancer can be connected with inflammation of the genitourinary tract.Materials and methodsIn years 2006–2010 vaginal swabs from 452 patients were examined. 39 women with positive S. aureus cultures were analysed.ResultsComplications and interruptions during radiation therapy were observed in 7 (18.9%) of 37 patients with positive vaginal S. aureus culture. One of them, a 46-year-old woman developed pelvic inflammatory disease. None of the six patients who received palliative radiotherapy showed interruption in this treatment. Isolated S. aureus strains were classified into 13 sensitivity patterns, of which 8 were represented by 1 strain, two by 2 strains and three by 13, 8 and 6 strains. One strain was diagnosed as methicillin resistant S. aureus (MRSA).ConclusionsThe results of the present study show that S. aureus may generally be isolated from the genital tract of female patients with neoplastic disease of uterus but is not often observed as inflammation factor of this tract. Comparison of species’ resistance patterns may be used in epidemiological studies in order to discover the source of infections and therefore be of profound significance in the prevention of nosocomial infections.     

Baseline Karnofsky performance status is independently predictive of death within 30 days of intracranial radiation therapy completion for metastatic disease

IntroductionFor patients with brain metastases, palliative radiation therapy (RT) has long been a standard of care for improving quality of life and optimizing intracranial disease control. The duration of time between completion of palliative RT and patient death has rarely been evaluated.MethodsA compilation of two prospective institutional databases encompassing April 2015 through December 2018 was used to identify patients who received palliative intracranial radiation therapy. A multivariate logistic regression model characterized patients adjusting for age, sex, admission status (inpatient versus outpatient), Karnofsky Performance Status (KPS), and radiation therapy indication.Results136 consecutive patients received intracranial palliative radiation therapy. Patients with baseline KPS <70 (OR = 2.2; 95%CI = 1.6–3.1; p < 0.0001) were significantly more likely to die within 30 days of treatment. Intracranial palliative radiation therapy was most commonly delivered to provide local control (66% of patients) or alleviate neurologic symptoms (32% of patients), and was most commonly delivered via whole brain radiation therapy in 10 fractions to 30 Gy (38% of patients). Of the 42 patients who died within 30 days of RT, 31 (74%) received at least 10 fractions.ConclusionsOur findings indicate that baseline KPS <70 is independently predictive of death within 30 days of palliative intracranial RT, and that a large majority of patients who died within 30 days received at least 10 fractions. These results indicate that for poor performance status patients requiring palliative intracranial radiation, hypofractionated RT courses should be strongly considered.     

The role of irinotecan in the treatment of advanced colorectal cancer

PURPOSE: The purpose of the study was the evaluation of efficacy and the side effects of irinotecan in treatment of advanced colorectal cancer. METHODS: The authors presented their experiences with irinotecan in the treatment of 10 patients suffering from advanced colorectal cancer. The dose of irinotecan was 350 mg/m(2) every 21 days. Seven out of ten patients have taken oral fluoroquinolon to investigate its effect on the incidence of febrile episodes in case of febrile neutropenia. Three out of ten patients did not receive any antibiotic. The authors have examined the efficacy and safety of the treatment. RESULTS: One complete remission was obtained. Authors describe the observed side effects and the administered supportive care against serious complications. DISCUSSION: Serious diarrhoea has not been found in case of these 10 patients. The diarrhoea caused by irinotecan can be stopped by loperamide. The authors give accounts of early and following results.     

Nd-YAG Laser in Lung Cancer

We administered 45 Nd-YAG laser treatments in 29 patients (18 men) aged 39 to 82 years who had lung malignancy; 26 patients had primary non-oat cell lung cancer and three had metastatic airway malignancy. In all, 25 of the patients had been previously treated with combination(s) of surgical procedure, radiation therapy and chemotherapy. Indications for laser treatment included endobronchial airway obstruction with uncontrolled cough, hemoptysis, dyspnea or unresolved atelectasis-pneumonia. Of 15 patients with partially occluded tracheobronchial airway tumors, immediate palliative relief was achieved in 13 patients and lasted one to six months after a single treatment. In this group there was one postoperative death related to respiratory failure and two patients subsequently died of massive pulmonary hemorrhage. However, of 14 patients with totally obstructed airways, immediate palliative relief was achieved in only five patients and this lasted three weeks to three months after a single treatment. In this group there were two postoperative deaths related to progressive respiratory failure; in one case it was associated with endobronchial combustion of the fiberoptic bronchoscope. All three patients in both groups who died of respiratory failure were in acute respiratory distress and terminally ill before the procedure. These findings suggest that Nd-YAG laser therapy may be most beneficial in patients with partially rather than totally occluded airways due to lung malignancy.     

Progress in the therapy of myelodysplastic syndromes

The progress in the therapy of the myelodysplastic syndromes has been far from spectacular during recent years. No currently available treatment has been shown to be consistently effective in producing sustained improvement in hematopoiesis or in delaying leukemic evolution. With regard to both quantity and quality of life, no other treatment has been proven superior to classical supportive treatment, with the possible exception of bone marrow transplantation in younger patients. While in selected cases anecdotal successes have been noted with the use of hormonal therapy, some differentiation inducers, e.g. vitamin A- en D-analogues, have not hold their promises in placebo controlled trials. Attempts to induce complete remissions in MDS with antileukemic treatment have usually been unsuccessful. Toxicity is substantial and a considerable proportion of patients fare worse with chemotherapy than with standard supportive care. Recently, a flood of reports has appeared on the use of biological response modifiers e.g. cytokines and growth factors in the treatment of MDS. Perhaps some of these hold promises for a new era in MDS, but the data are preliminary and no follow-up on long term survival is at hand.     

Experience with aprepitant in the prevention of nausea and vomiting caused by highly emetic chemotherapy of lung cancer

Approximately one half of cancer patients experience nausea or vomiting during chemotherapy containing high-dose cisplatin, despite the use of a corticosteroid and 5-hydroxytryptamine(3) (5-HT(3)) receptor antagonists. The addition of aprepitant, a neurokinin 1 receptor antagonist, improves control of emesis by a further 15-20%, and improves late phase symptoms (>24 h after chemotherapy). The cornerstone of standard first line lung cancer chemotherapy is high-dose cisplatin. Our experience with aprepitant in the chemotherapy of 10 lung cancer patients is described, who reported more than one episode of vomiting caused by chemotherapy despite the use of ondansetron previously. Aprepitant prevented acute and late phase oncoming vomiting in all 10 patients and acute and late phase nausea in 9 of the 10 patients. According to our experience on a limited number of patients, aprepitant may be of clinical benefit in the supportive treatment of lung cancer, in achieving better quality of life during chemotherapeutic cycles in these patients.     

Pre-radiotherapy daily exercise training in non-small cell lung cancer: A feasibility study

AimTo examine the feasibility of an individual, supervised, structured moderate-to-high intensity cycle ergometer exercise training immediately before radiotherapy in patients undergoing concomitant chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC).BackgroundLung cancer is the most common form of cancer. Despite significant advancements in therapy and supportive care it is still the leading cause of cancer-related death worldwide.Materials and methodsRandomized controlled study design; patients with NSCLC receiving concomitant chemoradiotherapy were recruited and randomly assigned to either the exercise (EXE) or the control (CON) group. Exercise training consisted of 20 min moderate-to-high intensity aerobic interval training 5 times per week (Mon–Fri) prior to radiotherapy. Secondary outcomes were assessed at baseline and after 7 weeks: peak oxygen consumption (VO_2peak), functional capacity (6MWD), pulmonary function (FEV1), psychosocial parameters (quality of life (FACT-L), anxiety and depression (HADS)) and cancer-related side effects (reported daily).ResultsFifteen patients were included. All patients completed a baseline test, while 13 patients were eligible for a posttest. The recruiting rate was 44.1% and the overall attendance rate to exercise was 90.0% with an adherence rate to full exercise participation of 88.1%. No adverse events or any unexpected reactions were observed during the exercise sessions. No significant differences were observed within or between groups from baseline to post intervention in any of the secondary outcomes.ConclusionThis study demonstrated ‘proof of principle’ that daily moderate-to-high intensity cycle ergometer exercise was feasible, safe and well tolerated among newly diagnosed patients with locally advanced NSCLC undergoing concomitant chemoradiotherapy. Larger randomized controlled trials are warranted.     

PALLIATIVE CARE, PUBLIC HEALTH AND JUSTICE: SETTING PRIORITIES IN RESOURCE POOR COUNTRIES

Many countries have not considered palliative care a public health problem. With limited resources, disease-oriented therapies and prevention measures take priority. In this paper, I intend to describe the moral framework for considering palliative care as a public health priority in resource-poor countries. A distributive theory of justice for health care should consider integrative palliative care as morally required as it contributes to improving normal functioning and preserving opportunities for the individual. For patients requiring terminal care , we are guided less by principles of justice and more by the duty to relieve suffering and society's commitment to protecting the professional's obligation to uphold principles of beneficence, compassion and non-abandonment. A fair deliberation process is necessary to allow these strong moral commitments to serve as reasons when setting priorities in resource poor countries.