|Year : 2012 | Volume
| Issue : 3 | Page : 255-259
Optimizing patient outcome: Of equal importance in the palliative setting
P Parikh1, P Narayanan2, GS Bhattacharyya3
1 Director of Clinical Research, BSES GH Hospital, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Kiran Majumdar Shaw Cancer Center, Bangalore, Karnataka, India
3 Department of Medical Oncology, Fortis Hospital, Kolkata, West Bengal, India
|Date of Web Publication||12-Dec-2012|
Director of Clinical Research, BSES GH Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Parikh P, Narayanan P, Bhattacharyya G S. Optimizing patient outcome: Of equal importance in the palliative setting. Indian J Cancer 2012;49:255-9
| » Introduction|| |
When facing a patient with the diagnosis of cancer, the focus of the healthcare professionals is to provide the right treatment at the right time to optimize outcome. Today, with the availability of several new cancer-directed systemic therapeutic molecules (including targeted therapy); the treatment options with clinically relevant benefit are increasing at a rapid pace. One has to glance at the popular guidelines to see that we are spoilt for choice. This allows us to offer several lines of effective therapy, even for patients with advanced-stage disease where cure is not a realistic option.
Under these circumstances, how do we plan the best way forward? We shall discuss the salient factors that need to be given due consideration in the era of individualized or tailor- made therapy.
Throughout this manuscript, we have taken the example of lung cancer since it is the commonest cancer worldwide (11-13% of all cancers) and less than 10% are operable at initial presentation.  This is because such patients usually present in advanced stage requiring cancer-directed systemic therapy whose aim remains palliation. Hence, this became the obvious disease to discuss while addressing this question. ,
Aim of treatment
Once the diagnosis of cancer is confirmed, and the staging workup is complete, the multidisciplinary team (tumor board) has to decide on what is the aim of treatment. It is a paradox that cancer is among the few diseases known to mankind that can actually be cured in its true sense (when we use the correct meaning of cure - to indicate no evidence of any residual disease, no further treatment requirement and return of normal life expectancy). Today, more than 50% of cancers in the western world are cured. In India, as well as most developing countries, this happens in only one-third of cases. This is because currently available "state of the art" knowledge is not optimally implemented. We must remind ourselves that in oncology, the first chance to cure the patient truly is the best chance. No wonder, outcome is better when a qualified, trained gynaeco-oncologist operates on a patient with ovarian cancer in a high-volume center as opposed to undergoing the same surgery by a gynecologist or a general oncologist in a community hospital.  Similarly, maintaining dose intensity has been proven to significantly improve the chance of cure in hematological malignancies (e.g., Lymphoma) as well as solid tumors (e.g., breast cancer). ,
Does that mean that all hope is lost for patients with advanced disease or relapsed disease? Fortunately, the answer is no! Today, we have evidence that cure is possible even after relapse. For instance, use of Cisplatin and VP16 make this possible in testicular patients after first relapse - the evidence having been documented to as far back as 1994. 
The next step is to discuss what are our options when cure, in its strictest sense, is not a realistic option? For such patients, improvement in overall survival still remains the primary goal. In some instances, patients will have what is now called operational cure (e.g. long-term symptom-free benefit and survival in chronic myeloid leukemia (CML) using oral tyrosine kinase inhibitors (TKIs)). , In today's era of personalized medicine, we have a bouquet of options that helps patients get substantial benefit in the form of improved quality of life (QoL) as well as conversion of the disease into chronic illness, with minimal clinically significant toxicities. This is possible in most of the common cancers, including but not limited to metastatic/advanced breast, prostate, head neck, lung, colorectal, gastric, renal, and cervical cancers. , Interestingly, a review of the literature suggests that patients with cancer are generally willing to face the prospect of major adverse events in exchange for small therapeutic benefits more frequently than health-care professionals and healthy people. ,,,, Specific studies included in the review showed that British patients with cancer were more likely to accept radical treatment with a minimal chance of benefit than healthy people, including physicians and nurses. , Similar results were found in Norwegian patients,  and a study conducted in Japan showed that patients with lung cancer were more likely to accept treatment for small benefits than patients with other respiratory disorders. 
Selecting the right modality
The fundamental modalities available in our armamentarium against cancer include surgery, radiation therapy, and cancer-directed systemic therapy. Tannock  has elegantly demonstrated the how standard of care is often not implemented, even in the western world.
Beyond the recommended guidelines (and there are several of them focusing on a slightly different part of a moving target), physician preferences play an important role. Similarly, urologists in USA focused on prolongation of survival whereas their counterparts in France treated patients with the aim of improving QoL. Can such decisions be taken by a single oncologist or without a detailed discussion with the patient? Let us take the example of locally advanced laryngeal cancer. Is there a trade-off between best overall survival and voice preservation?  When surgery and radiation therapy can provide similar outcome, how do we choose one over the other? A balanced scientific judgment of experts/peers and patient preference should be given equal importance. This requires a tumor board or a multidisciplinary team to arrive at a consensus after careful deliberations. ,
Selecting the right schedule of treatment
The reality is that no country can continue to increase spending on health care at the current pace in an effort to provide top-class treatment to all its citizens. In the UK, it is estimated that continuing in this manner will lead to healthcare costs requiring half the wealth of the nation by the year 2050, and has the potential to exceed the growth rate by as much as a factor of 3. ,, Hence, all stake holders are attempting to devise strategies to counter the spiraling costs of healthcare. This is particularly important for developing nations, where resources are limited, there is no free/government universal healthcare and patients have to pay for medical treatment. The magnitude of this problem is obvious from the fact that in India, out-of-pocket spending accounts for 78% of India's total health expenditures, with medicines representing 72% of that total. In fact, health-care costs currently amount to 10% of household expenses. This forces almost half (47%) of hospital patients in rural areas to finance their treatment through loans and sales of assets.  Most developing countries will have three broad socio-economic groups. At the bottom of the pyramid are those who do not know where their next meal is coming from. The focus for them should essentially be preventive rather than therapeutic. The small percentage at the top can afford the best treatment option and will seek out a center that can offer them expertise meeting their expectations. In the center is the middle class. They are educated, motivated, access the internet to understand their disease, and are increasingly bold enough to ask detailed questions about management choices. Our responsibility toward them needs to focus on specific approaches that give them a cost-effective solution. 
Understanding the treatment: Explain the various treatment options in a neutral manner showing graphs and figures while using a language that is demystified. Convey the message that we are willing to work together to provide the patient with the treatment selected based on his preferences.
Communication with the patient: Be wary of the real intention of "well-meaning" relatives. Often, the family comes to the physician with pre-conceived notions, especially if they are apprehensive about being offered a treatment path that does not match their paying capacity. People from different ethnic backgrounds tend to respond differently to news about cancer, a fact the physician needs to be cognizant of while developing appropriate communication strategies. Only then can we convey the fact that we care about the patient as a human being first.
Innovate for our setup: Using the power of scientific knowledge to schedule treatment in an innovative cost-effective way. The article from gujarat cancer research institute (GCRI) shows the benefit of a chemotherapy protocol that prolongs the duration of infusion of Gemcitabine (350 mg/m 2 intravenous infusion over 4h).  Its merits are also discussed in an accompanying editorial by Matjaz.  So we will restrict our comments to emphasize that this approach results in 66% of cost saving for an expensive medicine like Gemcitabine without compromising on treatment response/outcome, a crucial health economics benefit. 
Quality Generics: India is well-recognized globally for a plethora of innovations in the pharmaceutical sector. Having US FDA and EMEA-approved manufacturing facilities; we are able to provide bulk drugs, intermediaries, and quality generics to the rest of the world. However, not all generics are equal (We have experienced a chemotherapy drug being supplied to a government hospital at a price less than the cost of the raw material with the vial having 73% of the stated liquid content). Emulating the benefits of published results and successful outcome of treatment regimen in patients is possible only when using quality generics - a distinction that the experiences physician is able to make with ease.
Patient assistance to reduce cost: There is increasing interest among pharmaceutical companies to fulfill societal obligations by providing free or discounted medicines to the needy through patient assistance programs (Sparsh of Dr Reddys, GIPAP of Novartis, etc.). Certain non governmental organization (NGOs) are also bridging the gap by providing medicines to those who cannot afford them (Indian Cancer Society, Cancer Patients Aid Association, AmeriCares India Foundation, Cancer Aid and Research Foundation, etc.). For instance, the Indian Cancer Society's Cancer Cure Fund is making available Rs. 120 million for poor and needy cancer patients being treated at centers that meet their criteria. 
Governmental Policy: Recently, the Government of India has announced an ambitious scheme of providing free medicines to all.  When implemented, all essential medicines (more than 300 drugs) will be available for free through the public healthcare system to all the citizens of India - a commitment whose value is more than Rs. 24,000 crores over the next 5 years. Already, there are schemes in Andhra Pradesh, Tamil Nadu, and Karnataka where below poverty line (BPL) patients are provided multidisciplinary cancer treatments which are strictly evidence-based and monitored by government-approved oncologists.
Implementing the planned schedule
Maintaining dose intensity is important for optimizing outcome in all cancer patients, be it the curative or the palliative setting.
A report on Cervical Cancer from Barshi, Maharashtra is worth looking at. For the same disease, at the same stage and using the same modality of therapy, radiation oncologists were able to improve overall survival simply by ensuring that the patients completed the planned (and intended) course of radiation therapy. 
We have previously reported about the differences in outcome when cancer-directed systemic therapy is under the direct supervision of medical oncologists as compared to non-medical oncologists in the community setting.  In this study, chemotherapy given by Medical Oncology Department of a large Tertiary Cancer Center (Group 1-57.3% [43/75] patients) was compared to those receiving it in the community setting under nonmedical oncologists (Group 2-42.7% [32/75] patients). The median overall survival was better in Group 1 (13 months) as compared to Group 2 (6 months; P value = 0.004). 
This is clear evidence that response, outcome and survival is optimized only when qualified, trained and experienced medical oncologists give cancer directed systemic therapy (maintaining dose intensity), even for advanced disease in the palliative setting - Apt treatment delivered in the apt way by the apt person is essential and the watch word [Table 1].
Focus on supportive care
Just as the first chance to treat cancer is the best chance of cure, so also the art of oncology lies in preventing side effects. This is possible only if supportive care is administered in a timely manner. Most oncologists prescribe standard anti-emetics, drugs to smoothen infusions, and make judicious use of measures to prevent consequences of myelosuppression based on international (western world) guidelines.  But do we pause to look at the issues in the light of our existing scenario? It is futile to ask the patient to promptly report to the hospital in case of fever - when he is living in a rural area that is 8 h away from the nearest primary health center or 4 h away from the nearest medical shop. The cost of each event and activity integral to the management of febrile neutropenia is an eye-opener that is a good example. In USA, the cost of the hospitalization for this eventuality balances well with the cost of granulocyte colony stimulating factor (G-CSF) when given prophylactically; leading to its initial recommendation to be used only if the risk of febrile neutropenia was more than 40%. In the same context, the calculations in the Indian setting are strikingly different. For a patient living in slums under unhygienic conditions, the risk of getting life-threatening infections are very high. So is the cost of hospitalization and intravenous antibiotics. This is in contrast to the relatively tiny cost of quality generic G-CSF in our country. Hence, it would be unethical not to use prophylactic G-CSF in our patients. This stand has been vindicated when the NCCN guidelines for management of febrile neutropenia dropped the criteria for prophylactic use of G-CSF (commensurate with the reduction in the price of G-CSF, the recommendations for prophylactic use of G-CSF was also dropped to 20% risk of febrile neutropenia). In a similar manner, while developing countries still have to worry about chemotherapy extravasation, this is a non-existent problem for the western world. Hence measures to tackle this need to be evaluated and standardized in our settings, as we have demonstrated.
Medicine is not mathematics. This is because the mysteries and intricacies of the human body are still to be unraveled. Hence, the initial treatment plan should not be considered as cast in stone. It is vital that evaluation of patient responses (both efficacy and toxicity) at regular intervals should dictate next steps. The mental attitude of the patient and the support he gets from the family is the link that is often forgotten.  This will have an important bearing on the patient's ability to tolerate side effects. Fine tuning of the dose, co-prescription medication, extension of treatment schedule, and change to second-line therapy at the right time are part of the mid-course correction strategy that often do not get the importance they deserve. ,,
Role of Counseling
The importance of setting aside adequate time for counseling cannot be over-emphasized. If it is to be described in one word, it is "satisfaction." And this is applicable to all stake holders. The patient should be satisfied that he got the best possible benefit as per his preference (response, survival or QoL). The family members should have the satisfaction that the best was done for the patient (within the boundaries of their limitations without any guilty feeling). The treating oncologist should be satisfied that he first understood the patients' needs and then used his knowledge and skills to ensure that he chalked out as well as implemented a plan individualized to meet these expectations. There are two crucial factors that needs close attention. The first is to be aware that the patient (and family) might be wanting to convey their intention indirectly (e.g., "I don't want to put my family into debt while undergoing treatment" versus "I don't care how much it costs, but I want my patient to receive the best possible treatment"). The second is that during the discussions, the patient (and the family) will be able to understand and retain only a small fraction of what was discussed. Besides, they tend to latch on to words and sentences that they want to hear and then link them together in a manner that was not the original meaning. This leads to be nidus of misunderstanding, miscommunication, conflict, and all its consequences. It is a pity that formal oncology education does not teach effective communication, leaving most healthcare professionals to learn-on-the-job. Using a resource that can address this unmet need is a vital link in optimizing oncology management.
| » Conclusion|| |
Maintaining dose intensity is important for optimizing outcome in patients even in the palliative setting. ,, It has been previously shown that in advanced non small cell lung cancer (NSCLC), treated with cancer-directed systemic therapy, survival is directly related to the dose intensity of the therapy administered. The challenge is to ensure how this will be implemented. In a large country like India, (the situation is also the same in SAARC countries as well as other developing countries), the real-life situation is that oncologists help the local specialist manage the patient by providing long-distance guidance. Unfortunately, even when written protocol, instructions, and guidelines are given, community doctors did not maintain dose intensity, compromising on the outcome and survival. The local community specialists must realize the importance of following instructions of the oncologists strictly to optimize patient outcome. They should bury the misconception and assumed belief that cancer-directed systemic therapy, especially in the palliative treatment, can be given equally well by non-medical oncologists without compromising on patient outcome. With the recent court rulings and statement by the Director of Medical Education that it is "inappropriate for an MBBS doctor to administer chemotherapy," non-medical oncologists should be aware of the medico-legal risk in undertaking such a misadventure as well. 
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