I would like to officially welcome on board Dr. Rohit Malde, (Radiation Oncologist, Nanavati Hospital, Mumbai).
We both are colleagues here in Mumbai, and he is a part of our team. I must tell you, Dr. Rohit is a very meticulous person when it comes to his work, apart from being very well read and absolutely up to date with the latest stuff.
It's a pleasure to have Dr. Rohit on board. i am sure, members will get to learn a lot of things from him. Please feel free to ask him any questions that you may have.
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Thanks Sumeet for the official welcome and your kind words. Will try and contribute to this elite forum and help all esteemed members as much as possible.
Hello Kontak thankyou for your concern. As you know that the PET report was not very satisfactory I was put on oral chemo and hormone therapy but my stomach could not take it so I have been put on an injection every fortnight till March . I have sent a message to Dr. Sumeet regarding the injection but have not received a reply as yet, probably he is busy so am waiting for his reply. I have already taken the first injection will know of the outcome after March, 2015. you all I hope are keeping well . take care and a big hug to all.
Nice Question! Feel like sitting in yet another Exam facing difficult and tough questions.
Anyways ! Lets start with few basics, How does Chemotherapy & Radiotherapy work ?
All living tissues have cells which undergo 5 phases in their cell cycle, which you must be well aware ( G1, S, G2, M & G0 ), which both cancer cells as well as Normal cells undergo. Though chemotherapy cannot differentiate between cancer and normal cells, many chemotherapy drugs work on actively reproducing cells (which are not in G0 phase), while some work specifically on cells in S phase, or M phase. These characteristics matched with the cancer type, helps clinicians decide which drugs to use for which cancers and how best to schedule and use them.
Many chemo drugs which you are perhaps referring to (Alkylating agents) can damage the DNA in addition, as a result of which it can activate a proto-oncogene or result in inhibiton of the tumour supressor gene, disrupting this intrinsic milieu and culminate in a malignancy like leukemia or solid cancers some 2-10 years later.
This risk of chemotherapy induced secondary cancer ranges very widely from as little as 1% -15% based on age at which patient underwent chemotherapy, the chemotherapy drugs and their doses used, the type of cancer treated, whether multiple drugs were used or single drugs used, whether patient received additional radiation as well or not, etc. Childhood cancers are challenging as this risk of second malignancy is substantial, while cancers of the elderly age group, this is less meaningful.
Radiotherapy works predominantly by damaging DNA. This results either in single strand break or double strand breaks, the latter are much difficult to repair. Cancer cells are generally less differentiated and more stem cell-like; they reproduce more than most healthy differentiated cells, and have a diminished ability to repair sub-lethal damage. Radiation is given in small doses and normally given daily, the reason we give a gap of 24 hrs (minimum 6 hrs) is to ensure that normal cells regenerate and repair in that time frame, whilst there is very little repair exhibited by cancer cells.
Radiation induced cancers do not occur immediately after irradiation. Instead, surviving cells appear to have acquired a genomic instability through this repair process which causes an increased rate of mutations in future generations. The cell will then progress through multiple stages of neoplastic transformation that may culminate into a tumor after years of incubation. Currently, we cannot predict which patients are likely to have these Radiation induced cancers. But the therapeutic ratio of harm Vs Benefit is very evident, and hence unquestionably these treatments have stayed with mankind over the last century.
More so, those cancers that may develop as a result of radiation exposure are indistinguishable from those that occur naturally or as a result of exposure to other carcinogens and our current lifestyle of smoking, alcohol consumption, and diet, significantly contribute to this.Radiation induced leukemias may take 2-10 years, whilst solid tumors may clinically manifest after latent period of 10-15 years. Literature have documented cancers appearing as late as 40 years post Radiation, however the chances or probability are miniscule.
Proto-oncogenes and Tumour Suppressor Genes used to to be one of my favourite topics to read a decade back.
For the non-medical members, and to simplify things a bit, if this is going all bumper over the head, lets introduce this concept gradually.....
Proto-oncogenes – These are normal genes, that if activated by mutation results in abnormal signal transduction (via synthesis on an oncoprotein) resulting in an uncontrolled cell growth and proliferation (cell immortality) resulting in cancer formation
Tumour Suppressor Genes – These are normal genes, which are check point controllers, which normally synthesize a protein and inhibit cell cycle proliferation serving as a Gatekeeper. If there is a mutagenic event in this gene, the switch is put off, thereby resulting in uncontrolled proliferation of cells. (cancer)
Viral (predominantly) , very little bacterial (exception of H.Pylori implicated in gastric cancers) are implicated in Viral Oncogenesis.
Here what happens is, once a patient gets infected with the virus, the viral genome (DNA) may get incorporated into the human DNA, and if by chance or bad luck this gets inserted near a previously existing proto-oncogene in the genome of the infected cell, the virus causes overexpression of that proto-oncogene, which typically induces uncontrolled cell division can cancer. Damn ! ! !
Lastly, coming to the last question you ve asked, cancer mutagenesis is a multi step process.
Some cancers are caused by more than one gene, and some vectors, if used incorrectly, can actually cause cancer or other diseases. Replacing faulty genes with working copies also brings up ethical issues and no one knows the long term consequences of such therapies.
The concept of Gene therapy is not new, and in fact it was conceptualized as early as 1972. The principle is simple, we want to use nucleic acid polymers and gain access into the patients cell via a vector (like a virus), so as to either block the proto-oncogene or repair/replace the known mutational gene. Early clinical trials were all disappointing and unfruitful. More recently looking into a few success stories as treatment for non-malignant conditions like adrenoleukodystrophy, Choroideremia, Leber's congenital amaurosis, Lipoprotein Lipase deficiency, X linked Severe combined Immunodeficiency (SCID) & Hemophilia , there has been renewed interest in Oncology as well. Few early clinical trials (Phase 1) have shown few promising results at short follow up in Leukemias (CLL, ALL), Multiple Myeloma.
Glybera in 2012 became the first gene therapy treatment to be approved for clinical use in pts with Lipoprotein Lipase deficiency. The cost of this treatment is around $1.6 million making this the most expensive treatment in the world. Since the last 3 decades around 2000 clinical trials have been performed across the globe with limited success as you can see.
The story of Gendicine
In 2003, China became the first country to approve Gendicine as a gene therapeutic approach for patients with squamous cell Head & Neck region. With the media hype, this caught attention internationally and desperate patients and their relatives from Canada, US, UK imported this £ 1800 medication against their oncologists recommendation ( as this was not approved in Europe and US). When I was in UK, I came across one patient when I was at Bristol when a 49 year old IT executive surfed and expressed his wishes to undergo this treatment, which our bosses and hospital refused to deliver as it was not approved in UK and later I think he went private but do not know if he had it or not. In 2006, after the death of a famous personality called Jesse Gelsinger, the US authorites were forced to review the data and they established strong connections of the CEO, Dr Peng from SS Gen-Tech with the Chinese approval authorities and found insufficient information from the clinical trial and more so discovered that 652 adverse events were unreported, 6 unexplained deaths and virtually no scientific or medical information about this drug in the world scientific community. I do not know if this drug is still on the Chinese shelves and giant pharma companies were ever brought to justice.
All that glitters is not Gold !
The quest for an ideal gene therapy for cancer treatment is still on as we move into the 21st century. Not all hope is lost. Currently at best this should be regarded as experimental, and we should wait for official approval of such therapies till their long term consequences have been well studied from clinical trials. I will encourage patients to participate for such trials, if at all available, of course after understanding the risks and possible anticipated benefits, and their significant contribution to mankind for research.
I feel such treatment will be available perhaps in the next 5-7 years time, but fear that even if such a treatment was approved, it would surely be exorbitantly expensive and patented by large Giant pharma companies. Whether it would really be available for the common man or not, only time will tell !
For the time being, Chemotherapy & Radiotherapy are certainly here to stay as we improve the cancer outcomes and have a plethora of success stories through stories from Cancer survivors.
In the meanwhile, I would urge all members in this forum who are reading my article, please get yourself a decent Medical Insurance of at least 10 lakhs or so, as medical costs are spiralling rocket high and becoming unaffordable for the common man, were you to pay from your own pocket. It is disheartening to see here in India that patients cannot afford basic Chemotherapy or Radiotherapy, the inability of private setups to subsidise or reduce their costs any further beyond a threshold, and patients referred to government setups where at times the long wait leads to progression and inferior results of many cancers, which are treatable.
Phew !! Its been quite tiring just as we come out of an exam. !!!!
Jai Ho !
With best Wishes
Over & Out
Dr Rohit Malde MD, DNB, FRCR (UK)
Consultant Clinical & Radiation Oncologist
BNH HCG Cancer Centre, Nanavati Hospital (Vile Parle), Mumbai
WOnderful to read this. Very well explained, Rohit. And also, I can imagine the time it must have taken you to write all this. I salute your effort, buddy.
Hello Deep welcome on the forum. Your queries are all research based . Well, I saw your profile, I'm also pursuing research but not in Cancer, I've also done my Masters in biotechnology with internship in Immunology from IISc Bangluru. I wish to do a project on pesticide use and increasing breast cancer in rural India. For the same I need your support for many research based literature search and actual data.If you are agree to help me send me mail on sarika.biotech@gmail.com
Thanks doctor rohit for joining and supporting all of us.
Sir i want to ask that i had invasive duct carcinoma and had undergone 6 cycles of fFEC. I had taken 25 radiation and was also asked for 6 booster doses. I was given Blog means some patch was kept while giving radiation and due to that i had suffered allergy or infection and my radiation was stopped. I was not given booster dose. Sir will there any problem for me because of this or any treatment that i can take now for that
Hi Shirdi - feeling nice to see you on forum . Pl see to give more details what was the dose of radiation given so that Dr Rohit will help us in a more comfortable manner
Hi Shirdi - feeling nice to see you on forum . Pl see to give more details what was the dose of radiation given so that Dr Rohit will help us in a more comfortable manner
My apologies at the outset, as i am answering with very little information and making a lot of assumptions.
You ve had a Breast conserving surgery and you are probably node negative, and perhaps < 50 years and you were recommended Adjuvant Breast RT 50 Gy / 25 # / 5 weeks + Electron Boost 12.5 Gy / 5 # / 1 week
You had Bolus kept over your Breast during RT, and you developed Gr III / IV Moist Desquamation (skin reaction) as a result of which the RT had to be stopped.
(Please correct me, if i ve made any errors in my assumptions so far... but this is the amount of guess work which we have to make, when insufficient information exists)
You were treated most likely on a Linear Accelerator (LA machine) OR a ? Telecobalt machine.
Did you have Conventional Treatment OR 3 Dimensional Conformal Radiotherapy (3D CRT).
It is a bit difficult for me to comment why was a BOLUS used, and what was the dose distribution in the Radiotherapy plan generated by your oncologist.
If the time gap between stopping the Whole breast RT and Boost is < 2 weeks, your oncologist may give you the Boost, should there be adequate healing of the skin. If the desquamation, still persists, and gap > 2 weeks, it may be perhaps wise to omit the boost completely, as the probability of harm may overweigh the probability of benefit here, thereby putting you at an unnecessary risk of the possibility of late side effects of soft tissue necrosis/ fibrosis and Post Breast Therapy Pain Syndrome.
I know how you feel, as there was an initial plan to give you (x+y) treatment, and you ve had x, but not y..and you feel let down a bit. But, these are indeed difficult choices for your oncologist as well, who of course whats the best for you, but sees the ratio of Harm : Benefit perhaps slightly more clearly.
Primum Non Nocere
This is a latin phrase which means " First do no Harm " This is one of the guiding principle for physicians, that whatever the intervention or procedure, the patients well-being is the primary consideration.
This is what best i think your oncologist has just exercised.
Here is an article which describes that Chemotherapy can bring neurodegenerative diseases, and it happens with the application of chemotherapy drug 'Topotecan'. linkedin.com/today/post/art...
This thread is welcome Dr. Rohit Malde and for members to know him better. If you wish to discuss about any particular issues, such as the one you posted above, please start a new thread and not on this, please.
Also, if you are not aware, this forum is NOT a medical forum, to discuss complicated matters and drugs and such. This forum IS a patient and caregiver oriented forum, where we aim to help out people undergoing the journey of cancer, give them support, help them make choices.
For the threads you wrote above, including the one on Ebola virus, was ABSOLUTELY out of context for this welcome thread, and at least 15 members (yes, 15 members), sent me a personal message to delete your threads, as they were disturbing the harmony of this thread. Dr. Malde is a very busy person. He was very kind enough to reply (such a long reply) and such apt. You should have stopped there, however, you went on about discussing matters not in context of this thread. So i had to delete your thread, on request of so many members.
Please do not do it again. I understand your questions are absolutely valid, but this is NOT the right place to discuss them. The right place would be some medical forum and there are lots of them out there.
Deepraj - expect you will not write here the threads which are not relevant to the forum. We all are a community going under a very tough time - helping each other. If you cannot help us no problem - atleast do not waste the valuable time of our Doctors who are helping us without any monetary benefit
Hi, I am 39 years old, recently I did my routine ultrasono on both breasts and it says fibrocystic breast disease and advised me FANAC nd mamograhy.I also have little swilling i my left arm near armpit. and feek discomfort in the armpit. Last year my Mamo and ultrasono came out clear. I am scare and I dont have breast cancer in my famiy .i am mother of three. plz. Tell me in India where should I go for cancer treatment?
Your report looks fairly normal, nothing to worry about (if its fibrocystic disease). The best thing would be, to consult a specialist in your area. If you do not know whom to go to, you can even visit your gynecologist for a guidance. Since we are based in Mumbai, we can guide here, but outside of Mumbai we wont be able to guide you whom to visit and hence its safer to visit a doctor whom you already know.
And don't worry. This sure doesn't look worrisome to me.
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. Well, I saw your profile, I'm also pursuing research but not in Cancer, I've also done my Masters in biotechnology with internship in Immunology from IISc Bangluru. I wish to do a project on pesticide use and increasing breast cancer in rural India. For the same I need your support for many research based literature search and actual data.If you are agree to help me send me mail on sarika.biotech@gmail.com
Chemotherapy (TCH) given in specific order?
Chemotherapy induced neuropathy
Please help!! My mom is diagnosed with Breast cancer!
