Proposal Information for Osteosarcoma trial

Research proposal

An observational study of canine osteosarcoma in dogs receiving homeopathy as an adjunct to conventional treatment

Principal investigator: Geoff Johnson MA Vet MB MRCVS. VetFFHom. RSHom. PCH

Address: Wiveliscombe Homeopathic Veterinary Surgery, 12 North Street, Wiveliscombe, Somerset TA42JY

01984 624999

osteosarcomatrial@yahoo.com,

Summary

An observational study of 30 dogs suffering from canine osteosarcoma receiving homeopathic treatment as an adjunct to conventional treatment.  The survival times for dogs receiving homeopathy plus conventional treatment will be compared to established survival times of dogs receiving conventional treatment only (1,2,3,4). Survival time means from diagnosis to euthanasia.

This study will set up systematic scrutiny of treatment outcomes of 30 dogs referred by veterinary surgeons with a confirmed diagnosis.    Whilst no causative link between treatment and outcomes can be drawn from an uncontrolled trial, observational studies can provide useful information about what is occurring in practice (7). However results will be interpreted with caution, as higher numbers of participants are needed to overcome random effects in estimating the direction and magnitude of treatment effects.

Principal investigator

Geoff Johnson qualified as a veterinary surgeon (vet) in 1987, and subsequently qualified in veterinary homeopathy 1999.  He is the principal of a busy homeopathic veterinary surgery   in West Somerset.  He lectures frequently at home and abroad.  He wrote the curriculum and taught the Danish Homeopathic Veterinary Diploma which has just graduated nine vets.  He is one of the few UK vets who treat animals diagnosed with cancer using homeopathy.  He lectured conventional vets on this subject at the SW and London Vet Shows in 2014.

Potential impact on homeopathic veterinary research

If the results obtained with five dogs previously treated solely with homeopathy by the PI, can be replicated, then it will be become clear that homeopathy could offer potential for extending life for dogs diagnosed with canine osteosarcoma.

The PI’s aspirations for research into homeopathic treatment of dogs diagnosed with osteosarcoma are:

  • To improve the quality of life and to extend the life expectancy of dogs diagnosed with osteosarcoma
  • To provide further evidence of the efficacy of homeopathy in serious life threatening clinical conditions where conventional therapy alone has limited success.

Other Investigators

Other homeopathic vets who are members of the bahvs may also participate in the trial if the owner is unable to transport the dog to Somerset.

 

Osteosarcoma is the most common primary bone tumour found in dogs. It accounts for up to 85% of all malignancies originating in the skeleton. It mostly occurs in middle aged to older dogs, with a median age of 7 years..

It is very important to understand how far the disease has metastasised. Prognosis for canine patients with osteosarcoma depends on several factors. The average survival in dogs treated with surgery and chemotherapy is approximately one year (1,2,3,4). For dogs less than seven years of age with tumour located in the proximal humerus, the prognosis is very poor. Recently, a median survival time of seven months was reported for dogs receiving radiation therapy along with chemotherapy; whereas a combination of surgery and chemotherapy showed more encouraging median survival rates of 235-366 days with up to 28% surviving two years after diagnosis (4).  Dogs between seven and ten years of age have greater survival rates than younger and older dogs. In axial osteosarcoma, the medial survival rate is four to five months because of the reoccurrence of the disease and complete surgery is not possible because of the location (4).

Objectives of the study

The objective is to systematically record the life span of dogs diagnosed with osteosarcoma receiving homeopathy as adjunctive care to conventional treatment regime and to compare these results with the most authoritative data available on conventional survival times, subject to variables such as site, stage and size of tumour, metastasises, age of dog, and chemotherapy agent/s. The results will be written up and submitted for publication to a peer review veterinary science publication.

Trial design

Observational study of individualised homeopathic treatment of 30 dogs referred by veterinary surgeons with confirmed diagnosis of osteosarcoma.  The study is due to close after 24 months.

Inclusion criteria

Dogs with diagnosis of osteosarcoma confirmed in the last three weeks by the referring vet. Diagnosis of osteosarcoma will be confirmed by a specialist vet’s report based on clinical signs and imaging. Histopathology results will be recorded but are not mandatory.

Dogs in the study will be receiving conventional treatment from the referring veterinary surgeon.

Dogs on palliative conventional treatment only i.e. painkillers such as NSAIDS and opiates.

Owner’s agreement to attend two consultations (minimum) at Wiveliscombe  or Wetherby with the dog and to provide feedback on the dog’s progress.

Exclusion criteria

Concurrent disease, reported by owner or referring vet or identified during physical examination, that is likely to prevent the dog from living one year, and dogs with evidence of gross metastatic disease.

Ethics

This study observes routine practice with no additional risk to dog or owner.  Procedures are in place to ensure that observation for research purposes is conducted according to the highest ethical standards. The PI contacted the RCVS in July 2016 to let them know the trial is taking place

 

 Methods

All referrals will be made direct to the PI who will interview the owner over the phone or by email and the PI will complete a pre-entry assessment questionnaire (to include diagnostic information site, size and grade of primary tumour, metastases, conventional treatment). At this stage the PI will answer owner’s questions. Owners of all dogs meeting the inclusion criteria will be invited to attend the surgery for a 90 minute consultation with the dog and to supply a copy of the specialist and referring vets’ report.

The pre-entry assessment will be checked at the start of the consultation. Dogs not meeting the inclusion criteria will be offered appropriate care or referral.

The most appropriate homeopathic remedies will be prescribed.

After first and second consultations, telephone and/or email contact will be maintained to ensure continuity of treatment.  It is anticipated, subject to clinical need, that the second consultation will be conducted approximately four weeks after the first. Further consultations will be offered according to clinical need or for review. A follow-up form will be sent to owners who cease contact before the dog’s death.

All dogs will continue under the care of the referring vet, who with the owner will remain in charge of the decision making regarding euthanasia.

Outcome measures

Primary:  Survival time (ST) defined as the time from identification of first clinical symptoms until death or euthanasia

These results to be compared with current data available on ST and DFI for conventional treatment regimes.

Survival times  are available from these authoritative sources (1,2,3,4). These resources will be reviewed and updated before commencing data analysis. Comparative data will take into account variables such as site, stage and size of tumour, metastasises, age of dog, and chemotherapy agent/s.

Whilst quality of life (QoL) in cancer care is a very important aspect of welfare and validated tools are available, this measurement has not been included in this study as homeopathy treatment is offered as adjunctive to conventional care.  QoL results would be subject to individual dog’s post-operative recovery, tolerance of chemotherapy, and some owners not wishing to pursue the conventional treatments offered.

Power calculation

This observational study builds on the existing anecdotal evidence. With this level of evidence and for the purposes of an uncontrolled study, a power calculation is not possible. N=30 is a pragmatic figure based on the feasibility of recruitment and management of the cases.

Statistical analysis

The results will be tabulated and time to euthanasia will be compared to the most authoritative data available on conventional survival times subject to variables such as site, stage and size of tumour, metastasises, age of dog, and chemotherapy agent/s.

Proposed:

Kaplan–Meier survival curves (ref Bergman 1996, Vail 2002, Selmic 2014, London 2015).

and Cox proportional hazards regression (ref Selmic 2014, London 2015) to be used to compare  survival times (ST) and DFIs with current data available for conventional treatment regimes.

If sufficient numbers of participants enter the study with histopathology  results, their results will be analysed as a sub-group.

References

(1)   http://www.fitzpatrickreferrals.co.u HYPERLINK “http://www.fitzpatrickreferrals.co.uk/oncology-and-soft-tissue/canine-osteosarcoma”k HYPERLINK “http://www.fitzpatrickreferrals.co.uk/oncology-and-soft-tissue/canine-osteosarcoma”/onc HYPERLINK “http://www.fitzpatrickreferrals.co.uk/oncology-and-soft-tissue/canine-osteosarcoma”o HYPERLINK “http://www.fitzpatrickreferrals.co.uk/oncology-and-soft-tissue/canine-osteosarcoma”logy-and-soft-tissue/canine HYPERLINK “http://www.fitzpatrickreferrals.co.uk/oncology-and-soft-tissue/canine-osteosarcoma”- HYPERLINK “http://www.fitzpatrickreferrals.co.uk/oncology-and-soft-tissue/canine-osteosarcoma”osteosarcoma

Fitzpatrick Referrals founded in 2005 by Professor Noel Fitzpatrick and is the UK’s pre-eminent and largest dedicated small animal orthopaedic and neuro-surgical facility, employing over 200 veterinary professionals and comprising state of the art surgical, diagnostic and rehabilitation facilities.  This article explains osteosarcoma, and gives survival times as follows; Amputation and chemotherapy – 10 to 12 months, limb spare and chemotherapy – 10 to 12 months; radiation and chemotherapy – 8 to 10 months; amputation alone – 4 to 5 months; palliative care – 1 to 3 months.

(2)  http://vetspecialists.co.uk/factsheets/Oncology_facts/Ca HYPERLINK “http://vetspecialists.co.uk/factsheets/Oncology_facts/Canine_Osteosarcoma.html”n HYPERLINK “http://vetspecialists.co.uk/factsheets/Oncology_facts/Canine_Osteosarcoma.html”ine_Osteosarcoma.html

Davies Veterinary Specialists is one of the largest and most diverse small animal veterinary referral centres in Europe. Founded in 1998 by Dr Jerry Davies and his wife Olivia, DVS now employs more than 35 specialist clinicians, 60 nurses (many with an advanced nursing qualification), and 30 administrators and support staff.  This site explains osteosarcoma, its diagnosis, treatment and prognosis.  Stated survival times are; palliative therapy average survival time is approximately two months; if amputation is performed the average survival time is increased to six and a half months; palliative radiation and chemotherapy have an average life expectancy of six months; amputation with chemotherapy makes the average survival time just a little less than one year.

(3)   http://www.modianolab.org/cancer/cancer_osteosar HYPERLINK “http://www.modianolab.org/cancer/cancer_osteosarcoma.shtml”c HYPERLINK “http://www.modianolab.org/cancer/cancer_osteosarcoma.shtml”oma.shtml

The Modiano Lab at the University of Minnesota is working to find the causes for cancer, to understand the mechanisms that drive tumour behaviour and tumour progression, and, ultimately, identify the targets that will allow them to prevent, control, and treat different types of cancer. In partnership with the University of Minnesota’s Masonic Cancer Centre, they are also working to determine how cancers that occur in animals are similar to cancers that occur in humans, so that they can apply what they learn from our companion animals to people, and vice versa.  This article explains the diagnosis, treatment and prognosis of canine osteosarcoma.  It states the median survival time using chemotherapy combinations and amputation is 14 months.

(4)  Szewczyk, M., Lechowski, R., & Zabielska, K. (2015)  What do we know about canine osteosarcoma treatment? – review. Veterinary Research Communications39(1), 61–67. http://doi.org/10.1007/s11259-014-9623-0   http://www.ncbi.nlm.nih.gov/pmc/articl HYPERLINK “http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330401/”e HYPERLINK “http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330401/”s/PMC4330401/

This article is written by M. Szewczyk, R. Lechowski, and K. Zabielska from the Department of Small Animal Diseases, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-787 Warsaw, Poland.  The article draws on numerous references, describes osteosarcoma in its various forms, the risk factors associated with development, the diagnosis, various treatment options, and survival times.  To sum up, 72% of dogs with appendicular osteosarcoma treated by amputation alone died or were euthanized because of metastases after 138 days (from diagnosis).  Dogs treated with amputation and chemotherapy had a median survival time of 307 days.

(5) Johnson, G. (2014) The homeopathic treatment of cancer for animals.   Interhomeopathy (May)

This article written by Geoff Johnson (PI), presents three of his cancer cases;

  1. Canine stomach lymphoma diagnosed by specialist referral centre, treated with Gadolinium arsenate leading to complete remission after 3 weeks, with the dog asymptomatic after three years
  2. Canine oral epitheliotrophic T-cell lymphoma diagnosed by specialist referral centre treated with Aurum muriaticum and Kalium chlorosum, leading to full remission within 6 months and the dog asymptomatic after five years.
  3. Canine squamous cell carcinoma of the palate diagnosed by specialist referral vet treated with Symphytum 200c leading to dramatic reduction of tumour, as evidenced by the photographs. The dog, having been offered euthanasia, survived nearly 18 months before being euthanised because of a seizure.

(6) Johnson, G. (2011) A Case of Osteosarcoma. Veterinary Times

This article written by Geoff Johnson (P1) presents one canine osteosarcoma cancer case.  The dog presented from the primary vet with lameness and radiographic diagnosis of osteosarcoma and a prognosis of three months.  Phosphoric acid 200c was prescribed, and the dog survived 22 months, when the lameness recurred and the owner opted for euthanasia.

(7) Spence, D., Thompson, A., Baron, B. (2005)  Homeopathic Treatment for Chronic Disease: A 6-Year, University-Hospital Outpatient Observational Study. The Journal of Alternative and Complementary Medicine 11(5), 793–798.

This article records the outcome of homeopathic treatment in over 6000 people treated at the Bristol Homeopathic Hospital.