Author: Pine Street Foundation

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What should I eat during chemotherapy?

By Michael McCulloch, LAc, MPH, PhD
Article Current as of December 20, 2020

Essential issues to address, and a critique of available books

“In many ways, reforming American agriculture depends on rebuilding a culture of routine home cooking. I’ve come to think that cooking is a ¹political act, with large consequences not only for ourselves but for the environment and agriculture as well… Cooking is probably the most important thing you can do to improve your diet. What matters most is not any particular nutrient, or even any particular food: it’s the act of cooking itself. People who cook eat a healthier diet without giving it a thought.”[1]

-Michael Pollan, author of The Omnivore’s Dilemma and In Defense of Food

The goal of this article is to present tools you can use – and the evidence supporting them – to protect body weight and strength during cancer chemotherapy. The intentions with this goal are improving long-term treatment outcomes, reducing toxicity, helping complete the planned course of treatment, and improving overall quality of life.

Immune health, and the starts in the gut. The quality and composition of meals shape the balance and function of the biome, the microbes in your gut. This in turn affects the innate and adaptive immune functions of the immune system,[2] and the integrity of the body’s muscle mass.[3] Although cancer chemotherapy can substantially impact nutritional quality of life, taking action with appealing and healthful foods early in the course of treatment is an important way to minimize that impact. And, by combining foods with exercise – addressed in another upcoming article – you can protect and maintain your body weight and functional strength,[4] which will improve long-term treatment success.[5]

In this article, we address questions frequently seen in clinical practice, and include evidence from recent research:

  • How can chemotherapy affect nutritional health?
  • How to know if you’re developing – or at risk for – malnutrition during cancer chemotherapy? And, what tools can you use in tracking the results of your action plan?
  • What evidence-based cancer nutrition guidelines are available to you and your oncologists?
  • What questions are important to ask of your oncology team?
  • What observations of your health are important to report to your oncology team?
  • What books are available to help learn what to eat during chemotherapy, and how to assess them for taste appeal and evidence-based nutrition standards?

Questions like these are essential, and are not always adequately addressed during the very busy workflow of cancer treatment, and the distress of having a new diagnosis. This can lead to cancer malnutrition being overlooked in its early – and more treatable – stages.[6]

How does chemotherapy affect nutritional health?
When food intake is reduced due to nausea, vomiting, stomach pain, diarrhea and/or constipation,[7] weight loss can quickly develop, leading to loss of muscle strength.[8] Early intervention to prevent weight loss during cancer chemotherapy is essential, as a drop in weight by over 5% total body weight can adversely affect survival.[8] This occurs more often in men than women, and is also more likely if protein intake is reduced, and if there are significant medical problems in addition to the cancer.[9] Depending on the type of cancer diagnosed, weight loss can be seen in anywhere between 40% and 92% of cases. But, using nutrition and exercise to prevent or reverse muscle loss leads to improved survival[5] and improved overall quality of life.[10]

How to know if you’re developing – or at risk for – malnutrition during cancer chemotherapy? And, what tools can you use in tracking the results of your action plan?
Given the crucial importance of protecting body weight during cancer chemotherapy, accurate ways to measure and track weight are essential. Muscle loss can be already present, even if a patient’s nutritional status is stable, or they are overweight.[11] And, many chemotherapy drugs have higher toxicity when malnutrition and muscle loss have occurred: 5FU, Irinotecan, oxaliplatin, FOLFOX, cisplatin, capecitabine, epirubicin, taxol, sorafenib, safeni, vandetanib, pemetrexed, gemcitabine, vinorelbine, ribuximab, cyclophosphamide, doxorubicin, vincristine, and R-CHOP.[11]

Tools you can measure yourself (listed in order from lowest to highest accuracy):

  • Body Mass Index (BMI): This long-used measure is reasonably good for general health, but has only a 29% sensitivity (ability to detect) malnutrition during cancer care, when compared with PG-SGA, described below.

  • The simple question: “Have you had unintentional weight loss in the last 3-6 months?” This question is often used in oncology centers, only has 56% sensitivity in detecting malnutrition, meaning that over half of the time it fails to detect malnutrition that has already begun.

  • PG-SGA: The gold standard against which other tools to identify malnutrition are compared, PG-SGA, is accurate and only slightly more complex to use. There is also a newly available iOS app called Pt-Global.

  • The Malnutrition Universal Screening Tool (MUST): this new test has perfect agreement with PG-SGA (Cohen’s Kappa=0.79), is more straightforward to use,[6] and has been validated for use both in oncology, and in most other health concerns.[12] Click here for an online version.

Tools your oncology team can provide:

  • If you have had a CT-scan at the level of the third lumbar vertebrae: this targeted scan allows an accurate and specific way of examining muscle mass.[11]

What evidence-based cancer nutrition guidelines are available to you and your oncologists?
Medical practice guidelines for care are intended to harmonize clinical decision-making, thereby ideally helping improve outcomes. These typically come in two types: those that are evidence-based (developed using published research) vs. consensus-based (developed by experts based on their experience and approach to medical care).[13]

How well do patient exercise/nutritional guidelines work?
Some guidelines are tested to see if they make a difference, making them clearly evidence- based. One example is the American Cancer Society’s “Nutrition and Physical Activity Guidelines for Cancer Survivors”. In a large trial, 992 people diagnosed with Stage III Colon cancer were recruited after surgery, and provided with guidance on how to use exercise and diet to maintain weight during chemotherapy. They were also given questionnaires mid-way during chemotherapy, and 6 months after completion. This 6-point scale assigned 2 points each to body weight, exercise and diet.

  • Body weight: to get a score of 2, maintain BMI between 18.5 to 25;

  • Exercise: to get a score of 2, each week exercise at least 2 1⁄2 hours, and strength training twice weekly. For example, an hour of fast walking, 30 minutes of light strength training, and 1 hour of jogging; and,

  • Diet: to get a score of 2, eat 5 or more fruit/veg servings/wk, and eat only whole grains[5]

Those patients who maintained a score of 5-6 on the ACS scale, were 1/3 less likely to have recurrence after 7 years, and more than twice as likely to still be alive after 7 years.

What questions are important to ask of your oncology team when preparing for – or already receiving – chemotherapy?
“Do you have a team-based nutritional intervention program?”

Team-based nutritional interventions can make a difference in helping maintain body weight and quality of life. Two recent studies make this point clearly:

  • Detecting muscle and weight loss: A Cancer Nutrition Program set up at a French university cancer center screened 3078 people being treated for cancer, and discovered that 70% (that’s 2 of every 3) had cachexia, a problematic type of malnutrition and muscle weight loss frequently occurring in people with cancer.[14]

  • Preventing weight loss with a team-based intervention: In a study of 110 colorectal cancer patients receiving chemotherapy were randomly divided into two groups of 55 each. In the control group, a normal diet was provided. In the intervention group, individualized recipes were designed by a team of nurses, doctors, dietician, family caregivers, and the patients themselves. After the intervention, although there was no difference in body weight between the two groups,[15] there were improved levels in the blood of albumin, a protein which can predict cancer survival.[16] This team-based approach, therefore, provided important immune system changes which can help improve a person’s longevity.

Books helpful for learn what to eat during chemotherapy:

Tools used in assessing nutritional health:

“Malnutrition Universal Screening Tool” from BAPEN (PDF)

References:

1. Cooking: FAQ & Useful Links: https://michaelpollan.com/resources/cooking/

2. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI: Human nutrition, the gutmicrobiome and the immune system. Nature 2011, 474(7351):327-336.

3. Mareschal J, Achamrah N, Norman K, Genton L: Clinical Value of Muscle Mass Assessment in Clinical Conditions Associated with Malnutrition. J Clin Med 2019, 8(7).

4. Naito T, Okayama T, Aoyama T, Ohashi T, Masuda Y, Kimura M, Shiozaki H, Murakami H, Kenmotsu H, Taira T et al: Skeletal muscle depletion during chemotherapy has a large impact on physical function in elderly Japanese patients with advanced non-small-cell lung cancer. BMC cancer 2017,17(1):571.

5. Van Blarigan EL, Fuchs CS, Niedzwiecki D, Zhang S, Saltz LB, Mayer RJ, Mowat RB, Whittom R, Hantel A, Benson A et al: Association of Survival With Adherence to the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors After Colon Cancer Diagnosis: The CALGB 89803/Alliance Trial. JAMA Oncol 2018, 4(6):783-790.

6. Hettiarachchi J, Madubhashini P, Miller M: Agreement between the Malnutrition Universal Screening Tool and the Patient-Generated Subjective Global Assessment for Cancer Outpatients Receiving Chemotherapy: A Cross-Sectional Study. Nutrition and cancer 2018, 70(8):1275-1282.

7. Caillet P, Liuu E, Raynaud Simon A, Bonnefoy M, Guerin O, Berrut G, Lesourd B, Jeandel C, Ferry M, Rolland Y et al: Association between cachexia, chemotherapy and outcomes in older cancer patients: A systematic review. Clin Nutr 2017, 36(6):1473-1482.

8. Buskermolen S, Langius JA, Kruizenga HM, Ligthart-Melis GC, Heymans MW, Verheul HM: Weight loss of 5% or more predicts loss of fat-free mass during palliative chemotherapy in patients with advanced cancer: a pilot study. Nutrition and cancer 2012, 64(6):826-832.

9. Stobaus N, Muller MJ, Kupferling S, Schulzke JD, Norman K: Low Recent Protein Intake Predicts Cancer-Related Fatigue and Increased Mortality in Patients with Advanced Tumor Disease Undergoing Chemotherapy. Nutrition and cancer 2015, 67(5):818-824.

10. Mijwel S, Backman M, Bolam KA, Olofsson E, Norrbom J, Bergh J, Sundberg CJ, Wengstrom Y, Rundqvist H: Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial. Breast Cancer Res Treat 2018, 169(1):93-103.

11. Bozzetti F: Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy. Ann Oncol 2017, 28(9):2107-2118.

page12image3869120

12. Comparing Must and the NRI Tools in the Identification of Malnutrition in Heart Failure Patients DNP Projects. 36. [http://uknowledge.uky.edu/dnp_etds/36]

13. Djulbegovic B, Guyatt G: Evidence vs Consensus in Clinical Practice Guidelines. JAMA 2019.

14. Senesse P, Isambert A, Janiszewski C, Fiore S, Flori N, Poujol S, Arroyo E, Courraud J, Guillaumon V, Mathieu-Daude H et al: Management of Cancer Cachexia and Guidelines Implementation in a Comprehensive Cancer Center: A Physician- Led Cancer Nutrition Program Adapted to the Practices of a Country. J Pain Symptom Manage 2017, 54(3):387-393 e383.

15. Lin JX, Chen XW, Chen ZH, Huang XY, Yang JJ, Xing YF, Yin LH, Li X, Wu XY: A multidisciplinary team approach for nutritional interventions conducted by specialist nurses in patients with advanced colorectal cancer undergoing chemotherapy: A clinical trial. Medicine (Baltimore) 2017, 96(26):e7373.

16. Gupta D, Lis CG: Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J 2010, 9:69.

 

Categories
Featured Published Research Uncategorized

Coronavirus (COVID-19)

Here’s the latest on the Pine Street Foundation’s research on coronavirus (COVID-19).

RESEARCH PRESENTATION (May 14, 2020)
Michael McCulloch, LAc, MPH, PhD, the Pine Street Foundation’s Research Director, recently gave a presentation about COVID-19:

RESEARCH PRESENTATION (April 15, 2020)
Michael McCulloch, LAc, MPH, PhD, the Pine Street Foundation’s Research Director, recently gave a presentation about COVID-19:

RESEARCH PRESENTATION (March 19, 2020)
Michael McCulloch, LAc, MPH, PhD, the Pine Street Foundation’s Research Director, recently gave a presentation about COVID-19:

Click here for the slides used in this presentation.

Categories
Published Research

Omega-3 & Prostate Cancer Risk

JNCIIn 2013, the prestigious Journal of the National Cancer Institute published a paper purportedly concluding that fish oil supplementation increased risk of prostate cancer. In response, we have detailed the scientific reasons why the results of that paper were unlikely to be valid, particularly since they contradict current knowledge on this topic. The Journal of the National Cancer Institute accepted our paper and published it in 2014.

Please contact us to receive a copy of our paper.

Formal Citation:
McCulloch, MF, et al. (2014). “RE: Serum phospholipid fatty acids and prostate cancer risk in the SELECT trial.” Journal of the National Cancer Institute.

Categories
Uncategorized

Integrative Traditional Medicine and Chemotherapy: Survival Data in Node-Positive and Metastatic Breast Cancer

Published November/December 2001 in San Francisco Medicine

OUR DEFINITION OF INTEGRATION
Medical practitioners, East and West, search for a “magic bullet”-a cure that will revolutionize the practice and therapeutic value of medicine. While there is, as yet, no such single cure for breast cancer, there is growing evidence that “magical combinations” offer the most promise. An early example of a therapy that brought together separately investigated agents into one treatment for breast cancer was the CMF protocol as pioneered by Bonnadonna.(1)

Similarly, combination strategies have become the dominant practice in alternative medicine. The need for combination strategies has arisen out of clinical observations that single-agent alternative therapies for breast cancer are rarely successful. In our clinical practice at the Pine Street Chinese Benevolent Association, we provide multi-modality alternative protocols for patients with breast cancer being treated by nearby oncology specialists. We use Traditional Chinese Medicine (TCM) as the underlying organizing principle to design our protocols. In our experience, this integration can deliver more favorable results than either modality used alone. To illustrate these observations, we conducted a retrospective case review of 288 patients treated in our clinic between 1987 and 1991.

We report here 5- and 10-year follow-up data on these patients with node-positive Stage II and III, and metastatic Stage IV breast cancer.

PATIENTS AND METHODS
Between 1987 and 1991, we treated 288 women with breast cancer (Stage II: 109, Stage III: 86, and Stage IV: 93 cases). All cases were infiltrating adenocarcinoma, both ductal and lobular subtypes. Diagnosis and pathology were determined by:

  • observation and palpation of the breast mammography
  • fine needle aspiration
  • incisional or excisional biopsy
  • bone scan
  • estrogen receptor and progesterone receptor assay

All women received:

  • radical or modified mastectomy with lymph node dissection
  • adjuvant chemotherapy protocol. (CMF: cyclophosphamide, methotrexate and 5-fluorouracil for 6 months, or CAF: cyclophosphamide, doxorubicin, and 5-fluorouracil for 4 to 6 months.

In this retrospective review, our research goal was to examine whether a multi-modality protocol based on TCM integrated with CMF or CAF chemotherapy (vs. CMF/CAF alone) could increase 5-year and 10-year survival rates in women with stage II, III, and IV breast cancer. We selected as external controls patients treated with CMF or CAF alone, matched as closely as possible to our study cohort in age, estrogen receptor (ER) status, node status, use of Tamoxifen (TMX) treatment, and time the study was conducted.

We provided the same multi-modality protocol in all 288 cases. Close follow-up helped to achieve an estimated 95 percent patient compliance rate. Both the CMF and the CAF chemotherapy protocols were on a 21-day cycle. We also provided patients with the following description of our protocol design and rationale, based on TCM chronotherapy and clinically observed energetic patterns.

Part I -Days one through three of 21-day chemotherapy cucle. The goal is enhancing circulation to facilitate tumor drug delivery. Suggestions: relaxation, stress reduction, Qi-Gong.

Part II is days four through six. Chemotherapy has killed off numerous cells in the body, both cancer cells and normal cells. A salt and soda bath helps discharge toxins and drug metabolites through the skin: 1 cup of baking soda and 1 cup sea salt added to a warm bath. Soak for 20 to 30 minutes daily. Also helpful is dry skin brushing to stimulate and cleanse the lymphatic system. Use a long-handled natural vegetable bristle brush, passing over the skin in a clean sweeping motion (not back and forth) towards the heart. Avoid the face. This is done twice per day, before Qi-Gong practice.

Part III-days seven through ten. Numerous dead cells are piling up in the body and need to be removed. The white blood cells hit their nadir (lowest point). The amount of dead cells accumulating often exceeds the body’s natural ability to cleanse them out on its own. Therefore the main goal in this part is to assist the body in discharging and cleansing. In this way these dead cells will not be in the way of the next round of chemotherapy. Salt-and-soda baths and skin brushing continue, along with Qi-Gong.

Part IV-days 11 to day 21. During this time the blood counts and much of the body’s physiology will start to normalize. The goal at this time is to strengthen and enhance the immune system.

RESULTS
Comparisons In all disease stages, our multi-modality protocol appeared to compare favorably with other studies treating with either CMF or CAF alone (see TABLE I). We believe that the use of multi-modality protocols that combine surgery and chemotherapy with integrative TCM has benefited our patients.

DISCUSSION
Limitations This case review is a retrospective study, limited by availability of medical record data. Additional data such as the number of positive nodes per patient would have allowed us to make more specific comparisons. Furthermore, our Stage IV data have the potential for significant bias due to our not having available either the time from breast cancer diagnosis to first recurrence, or elapsed time from first recurrence to entry in our study.

By comparing our patients to those from other published studies using external controls treated with CMF or CAF alone, our study is subject to substantial limitations in matching study and control patients. Although CMF and CAF are similar in their efficacy, some studies show a slight survival and response trend in favor of CAF, (2,3) and others show a significant advantage. (4,5) Our findings may be more precisely rendered by comparing only those of our patients treated with CMF to the CMF external controls and similarly, for those patients treated with CAF.

We had some missing data in the CMF dosages, which could introduce some bias in comparing our patients to those treated with chemotherapy alone. Even though Pine Street patients were temporally matched to external control cohorts, and thus likely to have received similarly dosed chemotherapy dosages, differences in dosages could have biased survival outcomes in one direction or the other.

Matching patients was also made difficult by the varying percentages of patients in the control studies who had used Tamoxifen. Furthermore, a higher percentage of estrogen receptor positive patients were present in our Stage II (as compared to the Scottish study) and Stage IV study cohorts (as compared to the German study). This may have conferred a higher survival advantage to our patients. Note that when we aggregated our Stage II and Stage III patients in order to make a comparison with the Canadian study by Levine (in which more patients were ER-positive), there was a smaller survival advantage to our patients than in the previous comparisons.

Additional bias could be present due to the higher percentage of post-menopausal women in our study cohorts.

Our clinical practice focuses on the use of integrative protocols. With our own patients, we were not able to design a trial that would randomize patients to chemotherapy alone. A prospective study could help minimize the potential for bias through the randomization process.

Background Discussion:
Chrono-Therapeutics Every metabolic event undergoes rhythmic changes in time (thus, the term “chrono”). Drug bio-availability, host immunity and hormonal levels all demonstrate variability according to circadian rhythm. Early authors in the Chinese medical literature first described chrono-therapeutics as a treatment strategy in two Chinese medical classics: The Yellow Emperor’s Classic of Internal Medicine (Huang Di Su Wen Nei Jing)” and the Classic On Difficult Issues (Nan Jing).

In designing our protocols, we began with the original Chinese theories, adding where possible data on human physiological functions and drug pharmacokinetics from modern published sources.(6)

These protocols are based on a combination of traditional Chinese medical literature, clinical studies from Chinese journals, (7) published in-vitro studies, in-vivo animal studies, and published human trials. However, some protocol elements are not directly linked in the published literature with their intended uses as we have applied them. Although science has made considerable progress in the treatment of cancer, more progress is still needed.

We believe that “out-of-the-box” thinking in cancer care can combine published science, anecdotal observations and active patient and doctor collaboration to achieve better clinical outcomes.

Our clinical experience suggests that treatments timed according to the circadian rhythm may offer a long-term survival advantage. Our treatment strategies are based on the three-pronged principle of (1) boosting host immunity, (2) decreasing the body burden of drug metabolite toxicity and (3) enhancing the cytotoxic effect of chemotherapeutic drugs. Improving cancer treatment remains an important challenge. In future, we hope to formally test multi-modality protocols in prospective trials.

Pine Street Chinese Benevolent Association was established in San Anselmo, California in 1982. Pine Street houses a medical clinic, clinical research center, medical information library, and an Integrative Medical Tumor Board. Michael Broffman, LAc is clinical director, and Michael McCulloch, MPH, LAc research director. Other publications include a meta-analysis of TCM vs. alpha-interferon on the treatment of chronic hepatitis B (currently being reviewed by the British Medical Journal). Current research projects in progress at our nonprofit research office are formal survival analyses (breast, lung, colon, and stomach cancers), and the development of an early detection screening method for lung cancer using a professionally trained dog to detect exhaled volatile organic chemicals.

References:

Bonnadonna G, Brusamolino E, Valagussa P, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 1976;294:405-410.

Bonadonna G, Veronesi U, Brambilla C, et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst 1990 Oct 3;82(19):1539-45.

Falkson G, Tormey DC, Carey P, et al. Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer. Eur J Cancer 1991;27(8):973-7.

Buzdar AU, Kau SW, Smith TL, et al. Ten-year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol 1989;12(2): 123-8.

Gupta P, et al. Neoadjuvant chemotherapy with Cyclophosphamide, doxorubicin and 50-fluorouracil (CAF) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in 69 cases of locally advanced (stage IIIb) breast cancer. Jpn J Surg 1991 Nov;21(6):637-42.

Hrushesky WJ, Ed. Circadian Cancer Therapy. CR Press, Boca Raton, FL. 1994.

Chai KQ, Wang DY. The use of TCM differential diagnosis in reducing complications of cancer chemotherapy. Zhejiang Journal of Traditional Chinese Medicine 1997;32(10):472-3.

Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Scottish Cancer Trials Breast Group and ICRF Breast Unit, Guy’s Hospital, London. Lancet 1993;341(8856):1293-8.

Derman DP, Browde S, Kessel IL, De Moor NG, Lange M, Dansey R, et al. Adjuvant chemotherapy (CMF) for stage III breast cancer: a randomized trial. Int J Radiat Oncol Biol Phys 1989;17(2):257-61.

Andersson M, Lindegaard Madsen E, Overgaard M, et al. Doxorubicin versus Methotrexate both combined with Cyclophosphamide, 5-fluorouracil and Tamoxifen in postmenopausal patients with advanced breast cancer-a randomized study with more than 10 years follow-up from the Danish breast cancer cooperative group. Eur J Cancer 1999;(35)1:39-46.

Cocconi, G., G. Bisagni, et al. Comparison of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) with a rotational crossing and a sequential intensification regimen in advanced breast cancer: a prospective randomized study. Am J Clin Oncol 1999;22(6)?593-600.

Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1998;16(8):2651-8.

Reuters Health, November 15, 1999.

Sugiyama T, Sadzuka Y. Enhancing effects of green tea components on the antitumor activity of adriamycin against M5076 ovarian sarcoma. Cancer Lett 1998; 133(1):19-26.

Sadzuka Y, Sugiyama T, Hirota S. Modulation of cancer chemotherapy by green tea. Clin Cancer Res 1998; 4(1):153-6.

Zheng W, Dai Q, et al. Urinary excretion of isoflavonoids and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 1999;8(1):35-40.

Categories
Canine Scent Detection

Lung Cancer Detection by Canine Scent: Will there be a lab in the lab?

A team of researchers led by R. Ehmann at Ambulante Pneumologie (Stuttgart, Germany) have published an article in the current issue of the European Respiratory Journal reporting on a study in which trained dogs detected lung cancer with sensitivity of 90% and specificity of 72% [1]. Their well-designed study involved 60 lung cancer patients and 110 healthy controls, and is novel for also including ‘‘disease controls’’; 50 patients with non-malignant lung disease. The findings of EHMANN et al. [1] corroborate the results of an earlier study of canine scent detection of lung cancer, which reported sensitivity and specificity of 99%. Together, these two papers, which achieved high accuracy while using different dogs, trainers and human subjects, beg the question of where this might all be leading. The purpose of this article is to review the evidence for canine scent detection of human cancers, and focus on how these papers may help advance knowledge in the field of lung cancer. There are very few published data on canine scent detection of cancers in general, or lung cancer in particular, and they vary widely in accuracy achieved and disease studied. However, the high accuracy of canine scent detection of lung cancer suggests dogs might, in the future, make some modest contribution to successes in lung cancer screening and detection.

CURRENT METHODS FOR LUNG CANCER DETECTION FACE MANY CHALLENGES
The goal of accurate, safe and noninvasive methods to detect lung cancer in its early and curable stages is shared by patients, researchers and clinicians worldwide. However, lung cancer is all too often diagnosed at late stages. Lung cancer is the leading cause of cancer deaths across the European Union, both in terms of standardised mortality rates and absolute numbers of people dying [2]. In 2010, an estimated 220,000 new cases of lung cancer were diagnosed, and over 150,000 deaths occurred, making it the leading cause of cancer death in both males and females in the USA [3]. Early detection of lung cancer remains a challenge, despite recent evidence from the ongoing National Lung Screening Trial in the USA showing that lung cancer mortality can be reduced by up to 20% with low-dose spiral computed tomography (CT) screening com- pared to chest radiography [4].

While patients diagnosed with advanced lung cancer have a 5-yr survival rate of ,5%, survival can increase to .70% for patients whose disease is identified early when the lesion is small and localised [4]. However, at first diagnosis, over 75% of patients have advanced stage disease. Identifying lung cancer early is crucial to improve treatment outcomes and patient survival. The low sensitivity of chest radiographs, combined with the low specificity and high radiation dose of CT scanning, limit the reliability and safety of these technologies as screening tools. Furthermore, cumulative radiation exposure resulting from the use of repeated CT scanning can increase the risk of developing cancer [5].

EXHALED BREATH ANALYSIS: DOGS ARE ONE OF MANY DIFFERENT TYPES OF SCENT DETECTORS
An alternative strategy to lung cancer detection is the improved accuracy that can be gained from combining several tests as screening tools; one possible candidate may be the use of exhaled breath analysis.

There is strong biological plausibility to the idea of dogs detecting lung cancer in exhaled breath. Both our paper [6] and that of EHMANN et al. [1], in the current issue of the European Respiratory Journal, used an independent validation phase in which dogs were able to distinguish lung cancer patient breath samples from controls, using samples from individuals not previously encountered in their training. Nevertheless, critics may turn up their nose at the mention of using sniffer dogs.

This may arise in part because there are very few published data on canine scent detection of cancers in general (n58) [1, 7–13], or lung cancer in particular (n52) [1, 9]. The findings of these studies vary widely in accuracy achieved and types of cancer studied, and papers on either replication of early findings or screening trials have not yet been published [14, 15]. It can be said, however, that the high-quality papers among those published, in which the investigators used rigorous patient selection, sample handling and dog training methods, have shown promising results.

Work toward the development of an ‘‘electronic nose’’ for cancer detection has been underway for several decades; how-
ever, dogs still appear to be ahead in the race and seem to have sniffed their way to the front of the line. We recently published a systematic review of all known data on the evidence for cancer biomarkers in exhaled breath [16], and a limited number of other research teams have published pilot data on exhaled breath analysis in lung cancer. There are no agreed standards for of these methods has limitations hampering their use for highly accurate lung cancer screening, and none have achieved the high sensitivity and specificity seen with dogs.

DETECTING HUMAN DISEASE BY ODOUR HAS A LONG HISTORY
The first published report of detecting human disease in a specific organ system by odour appeared in a 3rd century BC Chinese medical text, the Nan Jing Classic of Difficulties.

‘‘[Every disease of the five solid organs is reflected in (externally observable) colour and smell. For diseases of the liver, it is a greenish colour and rank odour].’’

An earlier writing by Hippocrates (ca. 460 BC to ca. 370 BC) included a more general mention of odour changing in febrile patients in the medical text Prorrhetics II.

“[The (doctors) nostrils indicate much and well in (the case of) fever patients; the odours, however, differ a lot].”

Cancer detection by dogs
The first publication of a dog detecting cancer the case of a young female from the UK who remarked to a dermatologist examining a suspicious mole on her leg that her dog had been licking, nipping and barking energetically and persistently at the lesion [12]. The subject of this paper was then interviewed for a television documentary broadcast in 2006 in the UK [17]. Following the publication of our group’s lung and breast cancer paper [9], several dozen people have written letters reporting a similar story (data not shown).

A vision for the role of dogs in detecting cancer
Since we began our work in canine scent detection of lung cancer 10 yrs ago, we have frequently heard patients, clinicians and researchers lament about several critical issues at conferences, presentations and during scent trials: 1) the frustrations related to the slow progress in the forward movement of science, specifically with early detection; and 2) the anxieties caused by false positives and regrets resulting from false negatives, with current cancer screening and diagnostic methods. These com- ments from patients are understandable, given the frequent reports in the media about problems with lung cancer detection methods, whether it be the poor ability to detect lung cancer with chest radiographs, the hazards of cumulative radiation from CT scans, or the poor resolving power with small modules of the positron emission tomography (PET) scan.

However, imagine a future in which the term PET takes on a new meaning. Dogs could serve as an inspirational role, with the story of dogs detecting cancer in rigorous trials used as a friendly message to the public, perhaps encouraging patients who may be reluctant to seek medical help to do so.

Dogs could also serve a more pragmatic role. If enough funding were allocated to allow other research groups to replicate and refine the encouraging results of the two existing papers on canine scent extension of lung cancer [1, 9], dogs could be used as a noninvasive preliminary diagnostic screening tool or be used to help reduce false positives and false negatives of

existing imaging technologies. This would maximise the power of joint probabilities, similar to the combination of PSA and digital examination being more accurate than either method alone for detecting prostate cancer, or CA-125 and transvaginal ultrasound for detecting ovarian cancer.

In both the literal and the metaphorical sense, with the pub- lication of these papers on canine scent detection of lung cancer, dogs are once again demonstrating their ability to serve as protectors and guides. People worldwide feel a close affinity with the dog as a friend and protector. Whether or not sniffer dogs actually make it into the continuum of diagnostic evaluation has yet to be seen; their image could be employed in public health outreach for cancer screening, and may encourage people with worrisome symptoms to take earlier action. This would be a case of the dog acting as a shepherd; Lassie and Rin Tin Tin are still out there, looking out for our health.

STATEMENT OF INTEREST
None declared.

REFERENCES
1 Ehmann R, Boedeker E, Friedrich U, et al. Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon. Eur Respir J 2012; 39: 669–676.

2 Malvezzi M, Arfe A, Bertuccio P, et al. European cancer mortality predictions for the year 2011. Ann Oncol 2011; 22: 947–956.

3 Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277–300.

4 Aberle DR, Berg CD, Black WC, et al. The National Lung Screening Trial: overview and study design. Radiology 2011; 258: 243–253.

5 Sodickson A, Baeyens PF, Andriole KP, et al. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology 2009; 251: 175–184.

6 McCulloch M, Jezierski T, Broffman M, et al. Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integr Cancer Ther 2006; 5: 1–10.

7 Gordon RT, Schatz CB, Myers LJ, et al. The use of canines in the detection of human cancers. J Altern Complement Med 2008; 14: 61–67. 8 Horvath G, Jarverud GA, Jarverud S, et al. Human ovarian carcinomas detected by specific odor. Integr Cancer Ther 2008; 7: 76–80.

9 McCulloch M, Jezierski T, Broffman M, et al. Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integr Cancer Ther 2006; 5: 30–39.

10 Pickel D, Manucy GP, Walker DB, et al. Evidence for canine olfactory detection of melanoma. Appl Anim Behav Sci 2004; 89: 107–116.

11 Sonoda H, Kohnoe S, Yamazato T, et al. Colorectal cancer screening with odour material by canine scent detection. Gut 2011; 60: 814–819.

12 Williams H, Pembroke A. Sniffer dogs in the melanoma clinic? Lancet 1989; 1: 734.

13 Willis CM, Church SM, Guest CM, et al. Olfactory detection of human bladder cancer by dogs: proof of principle study. BMJ 2004; 329: 712.

14 Moser E, McCulloch M. Canine scent detection of human cancers: a review of methods and accuracy. J Vet Behav 2010; 5: 145–152.

15 Lippi G, Cervellin G. Canine olfactory detection of cancer versus laboratory testing: myth or opportunity? Clin Chem Lab Med 2011 [Epub ahead of print DOI: 10.1515/cclm.2011.672].

16 Szulejko JE, McCulloch M, Jackson J, et al. Evidence for cancer biomarkers in exhaled breath. IEEE Sensors J 2010; 10: 185–210. 17 Can Dogs Smell Cancer? Storyville. BBC television documentary 2006. Available from: www.passionateproductions.co.uk/film_can_dogs.htm

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Featured From the Board

Our 2012 Accomplishments

It’s been another fantastic year at the Pine Street Foundation…we’ve published peer-reviewed research, presented papers at conferences, received lots of media coverage in the national press, hosted community events, and made huge strides with all our other ongoing research projects. Here are some of the highlights:

Colon Cancer and Chemotherapy
We have been awarded a $70,243 one-year research grant from the prestigious Institute of East-West Medicine of New York to conduct a meta-analysis in which we will systematically identify all published randomized trials that provided patients who have colon cancer with Chinese herbs in combination with their chemotherapy. We will be looking for the impact of Chinese herbal medicine on both immediate results (do people using herbal medicine experience less damage to white blood cells or less drug toxicity?) and long-term results (do people using herbal medicine live longer after treatment and is their quality of life better?), as compared to treatment with chemotherapy alone. Click here to learn more. 

Canine Scent Detection of Cancer
We have been awarded a $100,000 two-year research grant from the prestigious Robmar Foundation to provide mentorship for other researchers and dog trainers working to train dogs in scent detection. We will expand our work in developing the Human-Dog bond, building on our prior work with ovarian cancer,  to also include lung cancer,  breast cancer,  and prevention of bladder cancer caused by chonically acute bladder infections in paraplegics. This establishes an important scientific requirement facing the field of canine scent detection in human health: replication of prior work by different groups working with different populations of patients. Click here to learn more.

Publication and Follow-up Presentations: Our Lung and Colon Cancer Survival Studies
Following official publication in December 2011, we spent 2012 presenting our work to clinicians and researchers across the country. These studies represented the results of ten years of treatment and follow-up for patients with lung and colon cancers and were the first to apply modern statistical analysis techniques to the analysis of data from patients treated with Chinese medicine for lung or colon cancer. We believe these papers will help set a new standard for rigorous analysis of data from non-randomized trials. Click here for more.

Clinical Advocacy for Patients with Cancer:
In collaboration with the Commonweal Retreat Center, we participated in a workshop and public presentation on the ways in which clinical advocates help people with cancer. Included in our presentations was a discussion of the past, present, and future of clinical advocacy, Pine Street’s approach to Chinese Medicine-based integrative care, and how to work with patients who are reluctant or are refusing conventional care. Click here for more.

How You Can Help
Whether you’ve known us since 1989 or have only recently discovered our work, it is important to note that the Pine Street Foundation is one of the most efficient and cost-effective research organizations of its kind in the country. And since the vast majority of all our funding comes from individual donors like you, your financial support truly helps us advance the field of integrative medicine and beenfits those in need of better treatments.

As you consider your year-end charitable giving, please keep the Pine Street Foundation in mind. Click here to make a donation now.

Categories
Canine Scent Detection

New Training Consortium: Leveraging Our Experience to Expand Our Reach

Tessy closes in on which breath sample was given by a woman with ovarian cancer
Tessy closes in on which breath sample was given by a woman with ovarian cancer

As part of our canine scent detection program, we are providing mentorship for other researchers and dog trainers working to train dogs in scent detection.

This work is supported by a $100,000 two-year research grant from the prestigious Robmar Foundation.

We are expanding our work in developing the Human-Dog bond, building on our prior work with ovarian cancer to also include lung cancer and breast cancer. This establishes an important scientific requirement facing the field of canine scent detection in human health: replication of prior work by different groups working with different populations of patients.

We are providing educational and mentorship support to other researchers and trainers involved in training dogs to use their sense of smell in evaluating human health, leverging our more than thirteen years of experience with canine scent detection, expanding our reach beyond what has already been achieved within our own group. As we move forward with our own research projects, we wish to provide significant mentorship to other teams doing the same type of work. In our mentorship of other teams, we provide:

  • Mentorship (helping other teams turn their visions into reality with concrete project design)
  • Scientific support (helping other teams write proposals, analyze data, and publish results)
  • Training support (helping other dog trainers become better scent detection trainers), and
  • Collaborative support (helping other organizations with project management and data auditing support).

Our goal is to expand our reach through this mentorship and research and to help other groups spread the word through publication in scholarly journals and through media exposure.

So far, we’ve provided mentorship to the following groups and institutions:

Anna Vikko, Dog Trainer (Kuopio Finland)
Asociación Humanitaria Para la Proteccion Animal de Costa Rica (AHPPA) (Heredita, Costa Rica)
Bellamica Pictures (Las Vegas, Nevada)
Canine China Search and Rescue Organization (Beijing, China)
Children’s Hospital (Boston, Massachusetts)
Dalhousie University (Halifax, Nova Scotia)
Dog Training Center for Search and Rescue (Slovenia)
Dutch Police Forensic Service (Zeeland, Netherlands)
Falco K9 Academy (Newcastle Co-Down, Northern Ireland)
Guide Dogs for the Blind (San Rafael, California)
Hawaii Canines for Independence (Makawao, Hawaii)
In Situ Foundation (Los Angeles, California)
Institute of Cancer (Lima, Peru) Massachusetts General Hospital (Boston, Massachusetts)
Massachusetts General Hospital (Boston, Massachusetts)
Norwood Hospital (Boston, Massachusetts)
St. Elizabeth’s Hospital (Boston, Massachusetts)
Thoracic Cancer Research and Detection Center Sheba Medical Center (Tel Hashomer, Israel)
Tufts University (Boston, Massachusetts)
Ulster Hospital (Belfast, Northern Ireland)

HOW YOU CAN HELP
Click here to make a gift (of any amount) to help support this project.

Categories
Chemotherapy & Antioxidants Headline Meta-Analysis

Chinese Herbal Medicine and Chemotherapy in the Treatment of Colon Cancer: A Meta-Analysis of Randomized Controlled Trials

We have been awarded a $70,243 one-year research grant from the prestigious Institute of East-West Medicine of New York to conduct a meta-analysis in which we will systematically identify all published randomized trials that provided patients who have colon cancer with Chinese herbs in combination with their chemotherapy.

Following our successful analysis of clinical trials testing combinations of herbal medicine and chemotherapy for lung cancer, we’re now turning our attention to colon cancer. In medical centers across Asia, patients being treated for colon cancer frequently use herbal medicine in combination with their chemotherapy. The Pine Street Foundation is now critically examining published studies to see whether Chinese herbal medicine, when added to chemotherapy, could measurably improve treatment outcomes for people with colon cancer, as compared to using the same chemotherapy alone.

WHAT WE PLAN TO DO
We will be looking for the impact of Chinese herbal medicine on both immediate results (do people using herbal medicine experience less damage to white blood cells or less drug toxicity?) and long-term results (do people using herbal medicine live longer after treatment and is their quality of life better?), as compared to treatment with chemotherapy alone.

We will also be looking carefully at the quality of the published studies. Most of the studies we have located in our systematic search of the medical literature were published in China and one of our goals with this meta-analysis is to better understand the level of scientific quality of these studies; many researchers in the Western scientific community have criticized Chinese studies for their low quality of design and reporting.

WHY THIS WORK IS IMPORTANT
By analyzing these studies, we’ll determine what study quality problems are most significant and where improvement is needed. Pine Street has three primary aims in conducting this meta-analysis. First, we are using the results of this study as a basis for designing a double-blinded, randomized trial for patients with colon cancer. Second, by pointing out where improvements in study methodology are needed, we hope to  contribute to the improvement in quality of clinical studies in China. Third, we want to educate readers outside of China on the vast quantity of research being conducted there, research that highlights the potential clinical benefits of integrative medical care.

CURRENT STATUS
We are in the final data analysis and manuscript drafting stage and expect to be publish this paper in 2014.

HOW YOU CAN HELP
Click here to make a gift (of any amount) to help support this important project.

Categories
Events Featured

Chinese Medicine for People with Lung Cancer: Treatment Results

In collaboration with the Commonweal Retreat Center of Bolinas, Calif., we participated in a workshop and public presentation on the ways in which clinical advocates can help people with cancer. Included in our presentation was a discussion of the past, present, and future of clinical advocacy, our approach to Chinese Medicine-based integrative care, and how to work with patients who are reluctant or are refusing conventional care.

Download (PDF, 2.37MB)

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Headline Pine Street in the News

Wellness Times

Pine Street in the Headlines

Service Dogs: A New Breed of Heroes

By Karolyn A. Gazella

Our canine companions continually remind us of their desire to serve and protect. Some do that as pets, but others make it their profession. Because of their keen sense of smell—which is up to 1,000 times more sensitive than human’s—dogs can be invaluable in searching for things undetectable to the human nose. “They toil daily on our behalf, snuffling out contraband, explosives and human bodies buried beneath tons of collapsed cement,” says Bill Benda, MD, who has written extensively about the healing power of animals.

But science is showing us that these beloved animals have abilities that go beyond airport security and into the field of medicine: “They can also detect covert cancer cells, or predict a hypoglycemic event or epileptic convulsion,” Benda says. Which begs the question: Is it time to put a Lab in the lab?

Click here to read the entire article.