CME article 4

 

Talk of Future in Oncology

Tumour Auto Regression and other Extra-Ordinary Responses:

A Libyan Experience

Dr. Manoj Sharma M.D. FICR* & Dr. Mabruk Ali Mohammed MRT,FRCR(I)**

Abstract

Spontaneous Regression of Tumour:

Definition Any histologically proven malignancy regressing completely/ near completely or partially, on its own without any known method of anti-cancer treatment or without ingestion of a known anticancer agent knowingly or unknowingly.

Tumour auto-regression is a well known phenomenon generally known to certain categories of histo-pathology types, There are various theories proposed for this auto-regression which are generally immunology based, hence reflecting the immunological status of the patient.

The observations of the authors, which included other than tumour auto-regression, are

  1. Extra ordinary radiation response of massive tumours even at 50%or less of the dose prescribed.
  2. very quick recovery from radiation injury or radiation induced morbidity.
  3. Extra-ordinary tolerance to peak radiation doses.
  4. long survivals with or without disease. It was also observed as total spontaneous regression with or without recurrence, which has occurred at the same or different site.

About 34 cases of different sites have reported in a short span of two years for a population of four million in the only cancer centre of Libya. 28 cases of various sites had shown total regression even at the 50% of the prescribed dose out of 300 cases treated that year. All the auto-regression cases had very high IgM and Interlukin-2 levels.

Other observations include detail description of Libyan food and life styles and herbs they use in their diet. A serious thought on anticancer agro-forestry. Author concludes the paper by giving a great emphasis on modern and indigenous immuno-modulator methods while radiation or chemotherapy is on or even in pre and post treatment period. Ayurvedic immunostimulants have found their established status in modern medicine labs. The delay is on our part to initiate or accept them for the greater benefit of the patients.

 

Introduction:

Spontaneous Regression of malignancy is one those intriguing phenomenon which puts a question mark in front of our present day understanding of malignancy with tools such as radiation, chemotherapy and surgery. One asks the question that if the tumours can regress on their own then why all these debilitating and devastating procedures? The points to ponder are as to what are those host (defence) mechanisms that are still unknown to modern science despite the understanding of cytokines, killer cell, interlukins and Clusters of Differentiation (CD). Why we are still in search of newer molecules of chemotherapeutic agents and newer radio active energies when there is an obvious tumour auto-regression without the interference by any of the above treatment methods.

The tumours are known to regress with radiotherapy or chemotherapy but recurrences at the same site or at distant sites are known. What fails then to permit what is known as "cell regeneration or tumour regeneration"? Why is the body not able to have a hold on these cells once their gross existence is removed? Or in other cases why the tumour despite such a large extent and size never recurs? Given the identical conditions of the known assessable clinical and lab parameters why the same type of tumour behaves differently in the different bodies. Geographical presentation of certain tumours is well known. Ruling out the etiological factors existing in those areas for a particular higher incidence and having a closer look at the dietary factors, what are the causes of lower cancer incidences in these areas? What are those host mechanisms other than the ones allegedly stimulated by the dietary factors that the cancer incidence is low in these areas. Is it by rule of omission towards a carcinogen and more ingestion of anti-carcinogenic food or is a long exposure to such dietary habits, which have boosted the host defence mechanisms. Can this fact be applied for a much wider application such as Cancer Prevention of population?

What could be those herbs, which are taken by the local populace over the passage of time for better health and longevity purposes?

If tumour auto-regression factors and host defence mechanism factors are well understood the effects of chemotherapy and radiotherapy can be made more sustainable for prolonged period.

In the author’s experience, the combination of Ancient Indian Medicine System

(Ayurveda) medicines have not only given better quality of life to the patients but also has helped great deal in faster recovery from radiation/ chemotherapy. It has also reduced the post radiation sequellae in all the cases. As a matter of fact the delay in recovery was identified by the author and always interrogate the patients if he/she is taking Ayurvedic rejuvenators- the answer invariably used to be "NO". In that case can these Ayurvedic rejuvenators form an integral part of dietary habits to give protection against myriad carcinogens in the environment? Can this luxury affordable by wise and rich few of the vulnerable population living in polluted metropolis or having vegetables irrigated by polluted rivers?

This paper tries to find out as to what could be those host factors or dietary factors which have resulted in such extraordinary incidences of spontaneous regressions of tumour and extra ordinary response to existing facilities to treat advance malignancy.

 

Definition:

Any histo-pathologically proven malignancy regressing, completely/near completely or partially on its own without any known method or anticancer treatment or without ingestion of known anticancer agents knowingly or unknowingly shall be categorised as spontaneous or auto regression.

All the cases included in this study were scrutinised prior to the inclusion on the basis of above definition.

Spontaneous regression is a well-known phenomenon and it very well documented. A ‘Medlar ‘review revealed that these regression reports on regression are generally sporadic or are pooled data.

Spontaneous regressions are commonly found in the following malignancies. In the order of most frequent tumours.

  1. Lymphoma(low grade groups)
  2. Renal Cell carcinoma.
  3. Melanoma and basal cell carcinoma
  4. Small cell carcinoma(lung)
  5. Neuroblastoma., Retino Blastoma

Theories of spontaneous regression

In the vast literature following theories are detailed:

1-CD4+ lymphocyte mediated.CD8+, Natural killer cells mediated

2-IgM antibodies mediate

3-Supression of oncogene expression and of host

4-supression of tumour expressed growth factors and receptors.

5-Lymphokine activated killer cells in conjunction with IL-2

 

There were yet many other reports available on tumour auto regression on assortment of tumour types such as

Angiosarcoma, Hepatomas, Squamous cell carcinoma, Osteogenic Sarcoma, neuroendocrine tumour, juvenile nasopharyngeal angiofibroma, neonatal fibrosarcoma etc.

 Material and Methods

The material of this paper are the patients seen in the ENT tumour Clinic, Oncology Clinic in addition to the cases seen in the Radiotherapy Department of Tripoli Central Teaching Hospital Tripoli LIBYAN ARAB JAMHIRIYA.

The cases reflecting the host immunity were studied and observed: under these headings

1-Spontaneous regression

2-Extra ordinary radiation response of massive tumours even at 50% or less of the

Doses prescribed.

3-Quick recovery from radiation injury or radiation induced morbidity after full

Dose in many as a rule.

4-Extra ordinary tolerances to peak radiation dose without general morbidity.

5-Exceptionally long survivors with or without disease.

 

The spontaneous regression was studied in two headings:

a) Total Spontaneous Regression

b) Initial spontaneous regression and then recurrence

I-at the same site, or

II-recurrence elsewhere.

 

Investigations

Barring initial few cases these cancers had their routine lab investigations and some special investigations such as Ig M studies and few cases had Interlukin-2 titres estimated though a kit.

Routine repeat biopsies were done to confirm it is a microscopic disappearance or morphologic regression .Few lymphoma cases were exception to this rule.

 

Observations

The total Libyan population is 4 million and the author in a short span of two years saw these 34 cases of auto-regression. Such a large number of auto -regressions were not seen by the author in his 15 years of carrier as an oncologist nor such phenomenon is known to his Indian Oncologist colleagues. All these auto regressions were biopsy proven with malignancies of varied histo-pathology. The split up of the cases is given in table–1.The table -2 shows the extra ordinary response in large lesions that were worth mentioning. To exemplify a segment of one year is taken. This is worth mentioning, as similar observations are not seen by many of us in India. The table -3 shows other observations on radiation morbidity patterns and radiation dose tolerance in these cases. The prolonged survival with disease was another factor observed in these cancer patients. The Table -4 shows the general impression on haematological parameters and special tests carried out to understand the phenomenon of spontaneous regression. Table-5 gives the ethnic, habit and habitat information. Table -6 gives information on Libyan diet.

 

Discussion:

The purpose of presenting this paper is to give a rather new direction in the thinking of a radiation oncologist. The frequency and varieties of tumour auto regression was indeed amazing and has raised a question mark in the very oncological concept of surgery, chemo and radiotherapy.

For a population of four million, this number was certainly high however for a Libyan oncologist it was not a matter of surprise! Rather it was a common observation over the years. When drawn attention, they always said with pride and smile "so what" They did not have any hard-core documentation but had umpteen case histories to narrate from their brain computer.

The review of literature reveals that spontaneous regression can happen in varieties of malignancies an immunological studies have shown several factors such as CD4+ and CD8+ T lymphocyte mediated, natural killer cell mediated, IgM suppresser killer genes mediated mechanisms. None of these could be studied in these patients due to various reasons.

However there are many other factors shown in various tables that suggest that the tumour regression can be greatly modified. Immunological strengthening of the patient is very important factor more so in the modern times. Indeed that is why we have agents such as interlukins, interferon and GCSFs etc. Many Ayurvedic immunostimulants have also started coming to lime light in the labs of modern medical institutes (IMS, BHU). Their role in the immunological aspect of diabetes has been established. These Ayurvedic stimulants are freely available in market. Chyavanprash, Amliki, Yogendra Ras Amritbhallatak are just a few to be mentioned.

Other associated observations made while irradiating these patients is of great significance to suggest very strong host defence and healing mechanisms in Libyan patients.

Epidemiological studies have shown that certain types of cancers are virtually non existent are of very low incidence in southern Europe which is abundant with olive, oranges, barley and yellow and green vegetables. Is it not high time for oncologist to begin a thought process for an anticancer agro-forestry by taking a policy decision on promotion of olive plantation, expanding the fruit production fields, re-introducing barley in Indian food, promotion of genetically engineered high lycopen tomato varieties from Israel, high beta carotene breeds of carrot and 1st but not the least frequent prescriptioning of Ayurvedic immunostimulants which have stood the test of time over centuries on humans. Lest these Ayurvedic stimulants are also patented under DUNKEL, just to be priced closed to Molgramostin, Interferon and inertlukin-2.

The discussion is incomplete without a talk on public cancer education on diet through media, which is persistently obsessed with scams, politic and share markets. Radiation surgery and chemotherapy will stay but the immuno potentiation has come in a big way, whichever path it may be-diet, Ayurveda, Agroforrestry, beta -carotene, bran, lycopen, Chyavanprash or if affordable interferon.

 

Conclusions

 

  1. Libyan people have shown astonishing tumour auto regressions.
  2. Libyans tolerance to radiation was extraordinary so was the response to radiation.
  3. Response to the treatment is not related to the treatment method used alone but there are several factors, which have been understood at the molecular levels.
  4. Great many factor remain to be investigated in relation to radiotherapy, chemotherapy and immunotherapy vis--vis serum immunological parameters.
  5. Immunological status has great role to play and it is high time a correct assessment of immunological status is done for Predictive Oncological purposes.
  6. The diet factor has a great role to play with the understanding of cancer epidemiolgy in certain geographical regions.
  7. It is high time a debate and a dialogue are started on anticancer agroforrestry: Promotion of green and yellow vegetables and fruits, Olive plantations and promotion of Ayurvedic herbs and roots.
  8. It is high time that the Indian Ayurvedic stimulants form the integral part of our prescriptioning at least to take care of the immuno suppression produced by the tumour, chemotherapy and radiotherapy.

 

 Observation Tables

Spontaneous Regression

Table -1

 

Site

Total Regression

Partial Regression

Recurrence

Elsewhere

1.Palate (1)

(Alveolar

Rhabdomyosarc.)

1(T3)

-

-

Lung(5)

(Sq. Cell Ca.)

3

1

 

 

-

Larynx (5)

Sq. Cell.. Ca.

2(T2)

1

-

Neck Nodes (2)

Sq. C. Ca &

Undf. Ca.

1

1

 

Lymphoma

Stg. I-II(5)

(Various grades)

5

2

2/5

BCC

8(T1-T2)

2

3/8

Cheek

(Sq.Cell.Ca.)

1(T2)

-

-

Nasopharynx

(Undiff. Ca.)

1 (T1)

1(T1)

-

Skin

(Sq.Cell. Ca.)

1(T1)

-

-

Uterine Cervix

Sq. Ce.Ca.

1

2

-

Total

_______________

24

______________

10

___________

 

Grand Total

34

 

 

 Table: -2

Extra-Ordinary Radiation Response even at 50% of the dose or even lesser dose (As if the titrated dose is not the textbook prescribed dose for these patients!) Period One year l989-90

Site

Total No of cases

T status

Radiation Dose Levels

10Cgy 20 Cgy 30 Cgy

Larynx

35

T2-1,T3-1

1(T2)

1(T3)

10(T3)

Nasopharynx.

30

T2-2,T3-1

-

1

2(T2+3)

Breast

42

T3-6

 

3

4(T4-1)

Lung

3Gyx10Hemith.+medias

50

T3-10

-

3

7

Basal C.Ca.

70

T3-4

-

2

2

Liver(MetS.C.Ca.)

17

Metastasis

 

1

1

Total

   

1

11

16

Grand Total=28 Out of the total 300 cases treated that year for all the malignancies.

 

 Observations

Table-3

Certain Gross Observations to Suggest Extra-ordinary Immune status.

 

Observation; -1

Wet Desquamation produced by 5000Cgy/5500Cgy given in breast has recovered within few days time quite unusual with Indian Patients.

 

Observation: -2

Full doses of 6500 Cgy to 7000 Cgy in Nasopharynx oral cancers

5000 Cgy to 5500 Cgy in Breast and Brain(200Cgy/Day)

5000 Cgy in Lung Cancers & 5500 Cgy in Bladder Cancers,

Were very well tolerated without any severe mucosal or dermal morbidity.

 

Observation: -3

Massive Disease (Nasopharynx, Breast, Lung, Bladder, BCC, Laryngeal Ca., with tracheotomy) cases were seen alive with or without disease for prolonged periods, viz. 2-3 years and even, more with sufficiently acceptable norms of fair quality of life.

 

Observation

Table-4

 

General Observations on other Haematological and Immunological Parameters;

1. - Haemoglobin levels generally above 14gm% and commonly 16gm%.

2- Total Serum protein levels are generally the higher side of the range or much above the range.

3-Immunoglobulins:

Ig G, Ig G IgM is generally on the higher sides

17 cases which could be estimated for IgM the titres were some where between 2mg?mlto 2.5 mg/ml of serum (normal range 0.5-2 mg/ml.

These levels have compared well with the normal controls who also had the similar levels,

 

Interlukin-2 Levels;

Titrated in 15 cases of auto regression have shown levels on the higher side when compared to controls.

 

Observation;

Table-5

Libyan Diet

Libyan Diet Constituted the Following;

1-Nonvegetarian food stuffs-Chicken, beef, mutton, fish, ducks, turkey, camel’s meat.

2a- Plenty of green and yellow vegetables in form of raw and cooked tomato (Lycopen!)

2b-Plenty of carrot and pumpkin in every traditional cooking (Spaghetti, pasta and Khous-Khous).

3-Usage of Barley and Gram (Bran +Malt)

4-Variety of all coloured fruits with plenty of species of each fruit.

5-Plenty of Almonds and abundant Dates.

6-Olive; Oil for cooking and processed fruit for eating with snacks or plain (Oleoresins, oleic acid!)

7-Over hundreds of varieties of citrus fruits, oranges etc. consumed in large quantities.

8-Parsley and Dhania (High Vit.C content) frequently used in cooking and salads.

 

Cows milk was recent arrival for last 20 years or so. It was sheep, goat or camels milk (Remember Gandhian therapeutics).

Traditional Herbs: Kleel, Zather mint leaves with medicinal values were used in the interior villages.

 

Observation

Table-6

Additional Information;

1-No Libyan was found under nourished or underweight at any stage

  1. Libyans are generally very healthy Greeko-Roman-Arab race and over weight in general.90% of Libyans live in coastal areas, which is abundant in fruits, vegetables, and olive and farm products.
  2. 3-Sexual performance and potency remained adequate with most of the males even with advance disease and during advance stages of radiation therapy or chemotherapy.
  3. Races who have migrated to cities have a history of leading tough life in harsh weather conditions of desert oven many, many generations and centuries.
  4. Ultra Modern medical facilities are available to a commoner for last 20 years or so hence lesser exposure to antibiotics .It was generally the survival of the fittest till two decades back. Infant mortality rates have fallen steeply.

___________________________________________________________________

 

 

Dr. Manoj Sharma M.D. FICR*

  • *Associate Professor of Radiotherapy, Maulana Azad Medical College, New Delhi and Advisor Cancer Control Programme Govt. of NCT of Delhi.

 

Dr. Mabruk Ali Mohammed MRT,FRCR(I)**

  • **Head, Department of Radiation Oncology and CT-scan, Tripoli Central Teaching Hospital, Tripoli, Libya.