Patient-centered care in cancer treatment programs: the future of integrative oncology through psychoeducation.

The reciprocal relationship between the mind and body has been a neglected process for improving the psychosocial care of cancer patients. Emotions form an important link between the mind and body. They play a fundamental role in the cognitive functions of decision-making and symptom control. Recognizing this relationship is important for integrative oncology. We define psychoeducation as the teaching of self-evaluation and self-regulation of the mind-body process. A gap exists between research evidence and implementation into clinical practice. The patients' search for self-empowerment through the pursuit of complementary therapies may be a surrogate for inadequate psychoeducation. Integrative oncology programs should implement psychoeducation that helps patients to improve both emotional and cognitive intelligence, enabling them to better negotiate cancer treatment systems.

The role of integrative oncology in a tertiary prevention survivorship program.

OBJECTIVE: Since 64% of cancer patients survive more than 5 years beyond diagnosis, oncologists are challenged to expand their focus from acute care to managing the long-term health consequences of cancer treatment and ensuring the integration of cancer prevention into their practices. This review defines the cancer prevention role of integrative oncology as a key component in survivorship programs. METHODS: A narrative review consisting of the results of preclinical studies, randomized controlled trials and systematic reviews that may contribute to cancer prevention. RESULTS: Integrative oncology focuses on the complexities of health and proposes a multitude of approaches. Its categories are mind-body techniques, physical therapies, nutrition plus supplements, and botanicals or natural health products. Behavioral modification, through selected integrative oncology interventions may enhance cancer prevention. CONCLUSION: Opportunities exist for oncologists to promote lifestyle changes that improve patients' length and quality of life. Integrative oncology utilizes techniques for self-empowerment, individual responsibility, and lifestyle changes that could potentially reduce both cancer recurrence and second primary tumors. Education in the principles of integrative oncology and evidence-based complementary therapies is lacking. There is a need for studies on cost-utility and effectiveness of whole systems programs of integrative oncology for the tertiary prevention of cancer.

Acupuncture as an evidence-based option for symptom control in cancer patients.

OPINION STATEMENT: Current technology suggests that acupuncture modulates neurological processes within the central nervous system, especially the spinal cord gating mechanisms, cerebral subcortical nuclei, and the hypothalamic-endocrine axis. Many single arm clinical studies report the effectiveness of acupuncture for controlling symptoms in cancer patients. However, the challenge has been to separate the nonspecific effects of the practitioner, as well as regression to the mean, from the neurophysiological effects of needle penetration. Recently, randomized controlled trials have attempted to answer this question, with mixed results. For example, needle penetration (or equivalent stimulation) is effective for nausea and vomiting, whereas it does not appear to be a major factor in reducing hot flashes. Safety and quality are priorities, so regulation of the practice of acupuncture is important, as well as excellent communication between practitioners. In addition, continuing research is mandatory, using validated methodology and reporting principles as outlined in the CONSORT and STRICTA recommendations.

Future directions for research on Silybum marianum for cancer patients.

Silymarin (Silybum marianum [L.] Gaertn. [Asteraceae]) is a promising agent for cancer prevention, adjuvant cancer treatment, and reduction of iatrogenic toxicity. Although it is safe and free of serious adverse side effects, few studies have evaluated its use alongside conventional cytotoxic therapies, and adverse events associated with long-term administration are uncertain. Although it may prevent some types of cancer, its promotion of tissue regeneration and its potential estrogen activity could promote the growth of some tumors. Further clinical trials using authenticated fractions of silymarin as simple and complex derivatives are required prior to any general recommendations. Future research should focus on authentication of active chemicals, pharmacokinetics, adverse interactions and quality control, prevention of cancer initiation and progression, adjuvant therapy for specific cancers, and prevention of toxicity from anticancer therapies.

Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire-RTOG Modification.

CONTEXT: The 15-item University of Washington Quality of Life questionnaire-Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG 0537. OBJECTIVES: This study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales. METHODS: EFA on the UW-QOL-RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability. RESULTS: The 15-item EFA of the modified tool resulted in 11 items split into four factors: mucus, eating, pain, and activities. Cronbach α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ ≥ 0.60) between consecutive time points and between total score and the Xerostomia Related Quality of Life Scale total score (ρ > 0.65). CONCLUSION: The UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items.

Targeting angiogenesis with integrative cancer therapies.

An integrative approach for managing a patient with cancer should target the multiple biochemical and physiological pathways that support tumor development while minimizing normal tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The authors will focus on natural health products (NHPs) that have a high degree of antiangiogenic activity but also describe some of their many other interactions that can inhibit tumor progression and reduce the risk of metastasis. NHPs target various molecular pathways besides angiogenesis, including epidermal growth factor receptor (EGFR), the HER-2/neu gene, the cyclooxygenase-2 enzyme, the NF-kB transcription factor, the protein kinases, Bcl-2 protein, and coagulation pathways. The herbalist has access to hundreds of years of observational data on the anticancer activity of many herbs. Laboratory studies are confirming the knowledge that is already documented in traditional texts. The following herbs are traditionally used for anticancer treatment and are antiangiogenic through multiple interdependent processes that include effects on gene expression, signal processing, and enzyme activities: Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (turmeric), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinale (ginger), Panax ginseng, Rabdosia rubescens (rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking on clinical trials. More data are required on dose response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as biological response modifiers and adaptogens, potentially enhancing the efficacy of the so-called conventional therapies. Their effectiveness may be increased when multiple agents are used in optimal combinations. New designs for trials to demonstrate activity in human subjects are required. Although controlled trials might be preferred, smaller studies with appropriate end points and surrogate markers for antiangiogenic response could help prioritize agents for the larger resource-intensive phase 3 trials.

A Phase I-II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy.

PURPOSE: Recent studies have suggested that acupuncture may improve radiation-induced xerostomia with an increase in the median salivary flow rate and sustained symptom relief. An acupuncture-like transcutaneous nerve stimulation method (Codetron) without invasive needles was developed to mimic acupuncture treatment. This Phase I-II study examined the effectiveness of Codetron in treating radiation-induced xerostomia. METHODS AND MATERIALS: Patients with symptomatic xerostomia after radical radiotherapy for head-and-neck cancer but with evidence of residual salivary function were recruited into the study. Two 6-week courses of Codetron treatment of acupuncture points preselected according to traditional Chinese medicine principles were given with a 2-week break between each course. Basal and citric acid-primed whole saliva production were measured at baseline and up to 1 year after treatment completion. Xerostomia symptoms were assessed by a five-item xerostomia symptom questionnaire with a visual analog scale and quality of life was evaluated using the Head and Neck Radiotherapy Questionnaire. RESULTS: We enrolled 46 patients in the study. All patients had received radiotherapy doses of >or=50 Gy to bilateral head-and-neck fields, including the parotid glands. Of the 46 patients, 37 completed the follow-up assessments at 3 and 6 months after treatment completion. No Codetron treatment-related complications occurred. Improvement in xerostomia symptoms was noted, with a mean increase in the visual analog scale score of 86 (p < 0.0005) and 77 (p < 0.0001) at 3 and 6 months after treatment completion, respectively. For all patients, the increase in the mean basal and citric acid-primed whole saliva production at 3 and 6 months after treatment completion was also statistically significant (p < 0.001 and p < 0.0001, respectively). No statistically significant change in the quality-of-life evaluation compared with baseline was observed. CONCLUSION: The results suggest that Codetron treatment improves whole saliva production and related symptoms in patients with radiation-induced xerostomia. The treatment effects were sustained for at least 6 months after Codetron treatment completion. A prospective randomized Phase III trial with appropriate controls is being planned.

Carcinomatous Meningitis: it does not have to be a death sentence.

Carcinomatous meningitis, specifically leptomeningeal metastases from solid tumors, has a dismal prognosis, with an overall median survival of 2 to 4 months. Lymphomatous meningitis has a better outlook, with a median survival of more than 6 months, but diagnosis may be delayed and treatment is not curative. Despite these poor statistics, there are subsets of patients who do relatively well. Moreover, there are a number of new approaches to the diagnosis and treatment of leptomeningeal metastases that promise to extend life and prevent disability. These include molecular techniques of diagnosis, expanding the repertoire of drugs available for intrathecal administration, using systemic chemotherapy to treat leptomeningeal disease, and applying strategies such as gene therapy and immunotoxins to the management of leptomeningeal metastases. These novel approaches offer the hope of liberating patients from a death sentence and providing clinicians with effective weapons in the fight against a dreaded neurologic complication of systemic cancer.

Randomized trial of hyperfractionation versus conventional fractionation in T2 squamous cell carcinoma of the vocal cord (RTOG 9512).

PURPOSE: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. METHODS AND MATERIALS: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. RESULTS: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239 patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. CONCLUSIONS: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.

Acute-phase response reactants as objective biomarkers of radiation-induced mucositis in head and neck cancer.

BACKGROUND: Current evaluation of radiation-induced mucositis in head and neck cancer relies on subjective scoring with interrater variability. We evaluated serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as objective markers of radiation-induced mucositis. METHODS: Weekly serum CRP and ESR levels were measured in patients treated for head and neck cancer with radiation ± chemotherapy. Acute radiation toxicity was evaluated using National Cancer Institute of Canada-Common Toxicity Criteria (NCIC-CTC) version 2.0 and the Head and Neck Radiotherapy Questionnaire (HNRQ). RESULTS: ESR and CRP levels were significantly elevated by 3 weeks (p = .01) and 6 weeks (p = .0002), respectively, and independent of age or pretreatment surgery. ESR was significantly dependent on radiation dose (p = .0004) and significantly higher with chemoradiation (p = .03). CONCLUSION: Serum ESR and CRP rise reliably in a radiation dose-dependent manner. ESR correlated with clinical symptoms and distinguished patients receiving chemoradiation. ESR and CRP may be an objective and sensitive marker of radiation-induced mucositis.

Systems modeling in integrative oncology.

Systems modeling provides an integrated framework to capture and analyze diverse and multidisciplinary data in a standardized manner. The authors present the Integrative Oncology Systems Model (IOSM) to help assess the impact of behavior modification and various therapeutic interventions on cancer development and progression and the resultant effect on survival and quality of life outcomes.

Can the therapeutic gain of radiotherapy be increased by concurrent administration of Asian botanicals?

Therapeutic gain by radiotherapy can be achieved through improved targeting, selectively sensitizing malignant cells, or protecting normal tissue. The majority of synthetic chemical radiation sensitizers and normal tissue protectors have proved to be too toxic at effective clinical doses. However, Asian botanicals (from both Chinese and Ayurvedic medicine) are being evaluated for their ability to improve therapeutic gain through the modulation of reactive oxygen species. An increase in the efficacy of radiotherapy on tumor tissue allows a reduction in the dose applied to normal tissues. In addition, some botanicals may selectively protect normal tissue or increase its repair following radiation therapy. The results are promising enough to consider clinical trials.

Vigabatrin-induced peripheral visual field defects in patients with refractory partial epilepsy.

PURPOSE: Vigabatrin can cause retinopathy, resulting in bilateral visual field constriction. Previous analyses of results from a prospective, observational study assessing vigabatrin-induced visual field constriction (described below) employed a partially subjective interpretation of static perimetery. To affirm these previous findings through more objective, quantitative methodology, we now report data from a subset analysis of refractory partial epilepsy patients in the study who underwent Goldmann kinetic perimetry. METHODS: Patients aged ≥ 8 years with refractory partial seizures were enrolled and grouped: those receiving vigabatrin for ≥ 6 months (Group I); those who had received vigabatrin for ≥ 6 months and then had discontinued for ≥ 6 months (Group II); and those naïve to vigabatrin (Group III). Patients underwent static or kinetic perimetry, or both, every 4-6 months for ≤ 3 years. For kinetic perimetry, the temporal and nasal visual fields were measured along the horizontal meridian with the largest (V4e, IV4e) and smallest (I2e, I1e) isopters, respectively. RESULTS: Of 735 patients enrolled, 341 had Goldmann perimetry data. Of these, 258 received vigabatrin. Sixteen percent of vigabatrin-exposed patients had moderate visual field defects (30-60° retained temporal vision), and 3% had severe defects (< 30° retained temporal vision). Visual function questionnaire results indicated a weak correlation between visual field constriction severity and visual symptoms. CONCLUSIONS: These results affirm both an analysis of the same study based primarily on static perimetry and findings from cross-sectional studies. The present analysis verifies that visual field constriction, when it occurs, is most often mild or moderate and is not associated with symptoms of abnormal visual function. The clinical decision to prescribe vigabatrin should be based on a benefit-risk analysis for each individual patient.

Phase II Randomized Trial of Acupuncture-Like Transcutaneous Electrical Nerve Stimulation to Prevent Radiation-Induced Xerostomia in Head and Neck Cancer Patients.

Current evidence indicates that acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) can provide sustained benefit for established radiation-induced xerostomia (RIX) symptoms. This is further being evaluated by comparing it with standard treatment (pilocarpine) in a randomized controlled trial. This report studies the potential effectiveness of xerostomia prevention using ALTENS delivered concomitantly with radiotherapy administered to head and neck cancer patients. Sixty patients were randomized to either the treatment group (n = 30) that received ALTENS daily with radiotherapy or the control group (n = 26) that had standard mouth care only. Stimulated and basal unstimulated whole saliva production (WSP) plus RIX symptoms visual analogue score (RIXVAS) were assessed at specific time points. Generalized linear models and generalized estimating equations were used for analysis. RIXVAS at 3 months follow-up after therapy completion was used as the primary study endpoint. The mean RIXVAS for the ALTENS intervention at 3 months was 39.8, which was not significantly different from the control arm value of 40.5. There were no statistically significant differences between the two groups for their mean RIXVAS and WSP at all assessment time points. In conclusion, there was no significant difference in mean WSP and RIXVAS between the two groups, so ALTENS is not recommended as a prophylactic intervention.

Vigabatrin for the treatment of infantile spasms: final report of a randomized trial.

A large randomized study was conducted in patients with newly diagnosed infantile spasms to compare 2 doses of vigabatrin in achieving spasm cessation. High (100-148 mg/kg/d) and low (18-36 mg/kg/d) oral doses of vigabatrin were evaluated in a randomized, single-blind study of 14 to 21 days with subsequent open-label treatment up to 3 years. Spasm cessation was defined as 7 consecutive days of spasm freedom beginning within the first 14 days, confirmed by video-electroencephalogram. A total of 221 subjects comprised the modified intent-to-treat cohort. More subjects in the high-dose group achieved spasm cessation compared with the low-dose vigabatrin group (15.9% [17/107] vs 7.0% [8/114]; P = .0375). During follow-up, 39 of 171 (23%) subjects relapsed; 28 of 39 (72%) regained spasm freedom. Adverse events were primarily mild to moderate in severity. Vigabatrin had a dose-dependent effect in spasm reduction. Spasm cessation occurred rapidly and was maintained in the majority of infants.

Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?

Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains about the efficacy and safety of this complementary treatment. Several randomized clinical trials have demonstrated that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatment-related side effects. Some data indicate that antioxidants may protect tumor cells as well as healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents. However, other data suggest that antioxidants can protect normal tissues from chemotherapy- or radiation-induced damage without decreasing tumor control. We review some of the data regarding the putative benefits and potential risks of antioxidant supplementation concurrent with cytotoxic therapy. On the basis of our review of the published randomized clinical trials, we conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.

Research on therapeutic massage for cancer patients: potential biologic mechanisms.

There is preliminary evidence that therapeutic massage is a useful modality for the relief of a variety of symptoms and symptom-related distress affecting cancer patients. Mechanistic studies are necessary to delineate underlying biologic and psychological effects of massage and their relationship to outcomes. The current article discusses a model for using nuclear magnetic resonance techniques to capture dynamic in vivo responses to biomechanical changes induced in the soft tissues by massage. This model enables study of the communication of soft tissue changes to activity in the subcortical central nervous system. We hypothesize that the therapeutic components of massage are twofold: (1) a rapid direct effect on local fascia, muscle, and nerves and (2) a slower delayed effect on the subcortical central nervous system that ultimately incorporates remodeling of plastic neuronal connections. This testable model has important implications for mechanistic research on massage for symptom control of cancer patients since it opens up new research avenues that link objective physiologic indices with the effects of massage on the subjective experience of pain and other symptoms.

Integrative oncology in North America.

Integrative oncology is an evolving evidence-based specialty that uses complementary therapies in concert with medical treatment to enhance its efficacy, improve symptom control, alleviate patient distress and reduce suffering. In North America the evolution of research into complementary therapies was delayed by the narrow focus of the Flexner Report. A government-funded research agenda and incorporation of complementary therapies into medical school curricula have been driven by early evidence of efficacy and patient demand. Integrative oncology focuses on the role of natural health products (botanicals, vitamins, and minerals), nutrition, acupuncture, meditation and other mind-body approaches, music therapy, touch therapies, fitness therapies, and more. Some natural health products, such as herbs and their constituent phytochemicals, may be biologic response modifiers that could increase cancer control. Current research stretches from the laboratory to health services. Institutions are exploring the effectiveness gap in their clinical services and are determining efficacy of complementary therapies through randomized controlled trials. Eventually, the goal is to establish practice guidelines through determining relative effectiveness and value through cost-utility studies. The aim of integrative oncology should be one medicine, not alternative; it should be patient-focused; it should be evidence-based; and it should provide the best care for cancer cure, prevention, symptom control, and quality of life.