Chapter ONE KDHS Kenya Demographics and Health Survery SSA Sub Saharan Africa MTRH Moi Teaching and Referral Hospital WHO World Health Organisation EBRT SBRT SF MR Definitions Metastases Pathological fracture Osteophilic Cancer Pain Uncomplicated spine metastases Titles

Chapter ONE
KDHS Kenya Demographics and Health Survery
SSA Sub Saharan Africa
MTRH Moi Teaching and Referral Hospital
WHO World Health Organisation
EBRT
SBRT
SF
MR

Definitions
Metastases
Pathological fracture
Osteophilic
Cancer
Pain
Uncomplicated spine metastases

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Titles:
A comparison of effectiveness of different cancer treatment modalities at MTRH in pain management of spine malignancies
Pain Control in Spine Metastases; a comparison of effectiveness of different cancer treatment modalities at MTRH
Keywords: Kenya, Cancer Pain, Spine Metastases, Treatment
Introduction:
The Cancer burden has become a huge steadily emerging Public Health concern that at large continues to receive minimal priority in Africa especially in the Sub Sahara even though the incidence of cancer in the region has markedly increased.(Kimani et al, 2017). In 2012 alone according to Parkin et al, 2014), the incidence of cancer in Africa was 6% (847000 new cases) with a mortality of 591,000 cases of which 75% of the global burden was in the Sub Sahara Africa. Prostate cancer in men and Breast cancer in women are the commonest cancer in the region. Furthermore, it is estimated that in the next decade more than 20 million people will be diagnosed with cancer annually with over 70% of the global death to occur particularly in the Sub Sahara Africa and other low income countries in which 82% of the world population lives (Kimani et al., 2017). This increase will therefore necessitate a huge demand for professionals in the care and treatment of cancer more importantly in cancer induced pain. However many Sub-Sahara countries have not yet prepared to address this epidemic. Thus there is a huge unmet need to scale up the uptake of cancer screening, early diagnosis, treatment and palliative care services in the region(Zubairi et al., 2017) (Kimani et al., 2017).

Data from the Kenya Demographics and Health Survey of 2014 also shows that cancer is the second leading cause of death besides cardiovascular disease among the non communicable diseases with a national case mortality rate of about 7%. The Kenya National Palliative Guidelines 2013 also estimates that over 28000 new cancer cases are diagnosed annually and 22100 people die of cancer each year. More so, Kenyans below 75 years are at a 17% risk of getting cancer and a 12% risk of dying from it (Ali, 2016). At Moi teaching and Referral Hospital the second largest hospital in Kenya, data extracted from the Eldoret cancer registry at Moi University estimated that about 5336 patients were diagnosed with cancer from 1996 to 2006. On average about 671 cancer cases were diagnosed annually. Solid tumours being the commonest in the region and accounted for 79% of the cancer patients however a slight difference in the pattern of the diseases was noted. Unlike elsewhere Ca. esophagus was the commonest cancer in the region while Ca. Cervix and Ca. Prostate were the commonest in females and males respectively. Hence therefore like elsewhere in the globe, cancer still poses a huge significant Public Health burden at MTRH and Kenya as a whole.(Tenge, Kuremu, Buziba, Patel, & Were, 2009)
On the other hand however, the bone is the third most common site of metastatic disease after the liver and lungs with the axial skeleton i.e. spine being the most commonly affected. A joaquim 2015 kassamali 2010 These metastases to the bone still possess a huge challenging orthopedic oncology problem despite the advances and innovations in treatment modalities today. Kassamali 2010XX) It is estimated that over 60 to 84 % of all metastatic cancer patients will eventually develop bone metastases and more than 40% of these will get spine metastases. a joaquim 2015 lee 2011 Annually approximately 5% of the cancer patients get spine metastases. kassamali 2010 Spine metastases are commonly associated with numerous Skeletal Related Events that chiefly include axial or radicular pain, pathological fractures, spinal cord compression and hypercalcaemia. These associated Skeletal Related Events pose a significant burden of morbidities in patients with spine metastases that they can adversely reduce the patients’ quality of life and consequently even shorten survival.lee 2011 With advances in cancer treatments, survival time has greatly improved even in patients with bone metastases which in return has lead to an increase in number of patients surviving with spine metastases and associated cancer induced bone pain. Curtin 2016 laredo 2017 a joaquim 2015
Spine metastases are most common in elderly patients. The age range for patients with spine metastases is between 40 to 60 years. Men aged above 60 are at a higher risk of getting spine metastases than women of the same age group.max 2003 These are usually patients with advanced cancers of the breast, prostate, lungs and or kidney that account for about 85% of all metastases cases. felice 2017 This stage usually marks the terminal stage of the disease where palliative care and pain control are the best holistic treatment approaches. (XXXXX) The role of palliative care here is not of a curative purpose but aims to improve the quality of life of the patient, assessment and treatment of pain and physical and spiritual problems. (WHO) Since pain is the most common and important morbidity in cancer patients with spine metastases xxxxxx, it is therefore important to adequately assess and manage pain in these patients because patient survival and improvement in quality of life have been greatly linked to optimal pain and symptoms control in cancer patients. (Milgrom 2017) Laredo 2017
With advances and innovations in the comprehensive cancer care and cancer treatment modalities (that is to say palliative radiotherapy, surgery, chemotherapy) in the globe, there has been enormous improvement in the ability to decrease tumor recurrence rates, quality of care and life, improve pain control and reduce the need of pain medications. Actually many cancer patients with spinal metastatic bone disease are now able to survive for long. The median survival for a patient with a solitary spine metastasis is more than 24 months compared to 3 months in liver metastases. Curtin 2016 felice 2017 However cancer induced pain remains the major symptom and cause of morbidity in these patients kassamali 2017 who often receive inadequate management for their pain which can be devastating to their quality of life. The breast 2013 Spine metastases are the commonest causes of this pain and worse still up to 85% of patients with spine metastases are estimated to be having varying degrees of pain. (Milgrom 2017) In 2017 K.N Kimani et al reported that one study conducted in Kenya found many cancer patients suffered with unrelieved pain which became increasingly intolerable as the disease advanced and as patients approached their end of life. And despite the fact that there has been increased globe awareness for cancer pain, little progress has been made in cancer pain treatment. vision
Numerous studies have broadly shown the effectiveness of these modalities in controlling and treating metastatic spine pain and their indications, benefits and limitations discussed in details. However few publications have tried to compare the superiority of these modalities over the others in controlling metastatic spine pain of cancer patients. Therefore it is significantly important that such a study be carried out to in order optimize pain management in cancer patients in a resource limited centre like MTRH as it is looking forward to establishing a comprehensive cancer care centre. Since at this stage of the disease the overall goal is usually to assess and treat pain, and restoring function during the remaining life span of the patient even though cure is usually not a realistic treatment outcome for spine metastatic disease. Nonetheless I am very confident that such a study will have a huge positive impact on the quality of life of patients surviving with spine metastases at MTRH.
With such limited resources at MTRH there is always a prior need to prioritize when choosing an optimal treatment modality for managing cancer induced pain hence for this reason it is always justifiable why such a study need to be carried out. This is solely because these treatment modalities still remain scarce and not readily available in the Sub Sahara. For instance K.N Kimani et al in 2017 reported that Africa has the lowest global coverage of radiotherapy with two thirds of its 277 radiotherapy machines located in only South Africa and Egypt. That only 5% of the cancer patients in the Sub Sahara have access to Chemotherapy and the region still has the lowest global consumption of opiods analgesics. Morphine consumption stands at 0.39mg per capita below the world average of 6.24mg. We can therefore note that a huge percentage of cancer patients in the region receive inadequate pain management even when cancer induced pain is a huge cause of morbidity and death. Therefore in order to give a general scope of this problem, evaluate the heath service for cancer patients at MTRH and be able to involve influence policy that will see the development of an integrated cancer care system in Kenya, I believe it is important that such a study evaluating the effectiveness of these modalities in pain management of patients with spine metastases at MTRH. I truly believe that this study will not only improve patient care but it will also provide a basis for future research in orthopedic oncology and pain control at Moi University and Kenya. It will also be of a very huge public significance which can attract further funding.
I must precisely state that even though the measure of pain in cancer patients is complex as in context it does not only entail the sensory component but rather also the psychosocial aspect of pain evaluation. (Willamson et al 2014). It is important to note therefore that for the purpose of this study I will only assess the clinical physical pain dimension alone and will exclude pain due to psychosocial factors such as fear, anxiety and depression. The effectiveness of a given cancer treatment modality will be evaluated and assessed basing on the patient’s response to pain which will be determined using the international consensus on bone metastases standards that account for changes in pain scores and analgesics use. ( GW. Paulien et al 2017, E Chow et al 2012)
Problem statement:
There is an increase in numbers of patients surviving with spine metastases today but unfortunately over 70 to 90% of these patients still chiefly complain of varying degrees of pain despite advances in cancer treatment modalities that have greatly improved patient survival and quality of care.
Justification
Even though Kenya has had a tremendous improvement in the uptake of cancer screening and early diagnosis prevention programs, many people are still diagnosed late when curative treatment is no longer an option. (KDHS 2014) Many of whom develop metastases but are still able to survive for long up to 24months in intolerable unrelieved pain with significant morbidities associated with spine metastases consequently living them incapacitated. Despite all this, the Africa Palliative Care Association estimates that only 3000 people in Kenya have access to palliative care and optimal pain management even when survival in cancer patients has been greatly linked to pain control. In a consensus to address this challenge, it is recommended therefore that a limited level centre like MTRH should readily have palliative radiotherapy and surgery. And more importantly patients should be followed up for pain control, spinal cord compression and pathological fractures. (The breast 2013) Unfortunately the availability of these treatment modalities has not yet reached an optimal level that patients’ cancer pain is often inadequately managed. In that review therefore this study looks to assess the effectiveness of the available treatment modalities at MTRH in controlling pain of patients with spine metastases. I believe that this assessment will not only identify an optimal modality but will also improve patient care, pain management and also be able to influence policy when prioritizing to choose a given treatment modality. Subsequently this will lead to the development of a comprehensive cancer care program. Based on the literature review I explored, numerous studies have illustrated detailed benefits, indications and limitations of each modality in managing painful spine metastases however scarce data exists comparing their effectiveness over the other in low resource centers. In order to address this problem, this cross sectional study will utilize cancer patients with spine metastases at MTRH and each will be assessed for pain outcome following a particular treatment intervention. Pain will be ranked using the Numerical Rating Scale.
Research Question:
How effective are the different cancer treatment modalities at MTRH in controlling pain of patients with spine metastases admitted at the hospital during a period of one year?

Objectives:

General objective:
The aim of this study is to compare the effectiveness of the different cancer treatment modalities at MTRH in controlling pain of patients with spine metastases admitted at the hospital during a period of one year.

Specific Objectives:
To determine the prevalence of spine metastases in cancer patients at MTRH
To identify the pattern of spine metastases among cancer patients at MTRH
To determine the prevalence of pain in patients with spine metastases at MTRH
To identify the commonest cancer treatment modalities for patients with painful spine metastases at MTRH
To compare the effectiveness of each cancer treatment modality in controlling pain of patients with spine metastases.

Significance of the Study:
I confidently believe that this study will provide a basis for development of specific guidelines for management and treatment of pain in patients with spine metastases at MTRH. The findings of this study research will explore the burden of pain in cancer patients at MTRH which I believe its evaluation will be very influential on policies of cancer pain management at MTRH. I anticipate that by achieving the objectives of this study, I will broaden on the awareness of pain as being a major challenge in cancer patients which will aid the hospital and University to prioritize palliative care services at MTRH. Subsequently this will increase and maximize on the number of cancer patients receiving adequate pain control and treatment at MTRH. Needless to say, this study will tremendously improve patient cancer care hence having a huge impact on cancer patients’ quality of life. Therefore in order to develop a comprehensive cancer care program the administration ought to prioritize when choosing a specific modality thus this study is significantly important to conduct since it aims to identify an optimal cancer treatment modality for controlling pain in spine metastases.

Chapter Two Literature Review
Introduction:
The International Association for the Study of Pain (IASP) defines pain as, “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” while according to Fields HL et al, 2005 “Pain is an unpleasant sensation localized to a part of the body. It is often described in terms of a penetrating or tissue-destructive process (e.g.: Stabbing, burning, twisting, tearing, and squeezing) and/or of a bodily or emotional reaction (e.g.: Terrifying, nauseating, and sickening)”. Both definitions above preciously classify pain into two major dimensions that is the Physical and Emotional aspects of pain. Since cancer pain is usually associated with psychosocial responses that may drastically affect a patient’s quality of life and this is so because more than 33% of cancer patients describe such pain as distressing and intolerable. In this context the absolute measure of pain in clinical studies therefore becomes a tremendous challenge that most research trials only focus on one aspect pain that is Physical or Sensory pain intensity. In this regard and for the purpose of this study I shall specifically be interest in the physical pain intensity and will exclude pain due to emotions or psychological factors i.e. depression, stress, anxiety etc even though it is as equally important when evaluating for pain in cancer patients. The measure of pain intensity is totally subjective and this is said to be the most successfully way of measuring pain intensity since pain has no direct link to the underlying pathology. Pain it is only influenced by its meaning to the patient and expected duration. “Pain is what the patient says it is” Williamson et al 2005.

Patterns and prevalence of Spine metastases
Spine metastases as an orthopedic condition present with different osteophilic properties in various patterns, prevalence and severity. With the advancement in the cancer care treatment modalities, many cancer patients are able to survive long and hence the prevalence of spine metastases in these patients has gradually risen. Later in the subsequent subtopics we shall realize who they different primary cancers influence spine metastases pain treatment and patients’ quality of life. But in order to best understand the morbidities caused by spine metastases in the surviving patients it is more important to first understand the pattern and prevalence of these metastases since they vary for different cancers, countries and age.
For instance in the USA is estimated that nearly about 300,000 cancer patients are living with bone metastases but more importantly to note here is that 60% of metastases are spine metastases Spratt, Daniel et al. 2017. While in the USA the leading spine metastases are secondary to breast, prostate and lung cancer in that order, this is not the case in the UK where the leading spine metastases originates from breast, prostate and thyroid cancer (Phanphaisarn et al, 2016. (Takagi et al., 2015) while evaluating Skeletal Metastasis of Unknown primary origin a quote that most spine metastases were secondary to lung, prostate and liver and the mean age for developing bone metastases was XXX. Further still another study in South Korea evaluating the pattern of metastatic fractures of the spine also shows a variation in the pattern of the common cancers that are mostly associated with spine metastases which cancers are mainly of Liver, multiple myeloma, lung and breast while the mean age for having spine metastases was 62.3% and occurred mainly in men. cho 2015.
In contrast though I expect a slight difference in this trend for cancer patients in western Kenya as data extracted from the Eldoret cancer Registry shows that Cancer of the Esophagus, Cervix and Prostates are the commonest in the region (Tenge et al. 2009) yet studies have shown that Cancer of Cervix (3.9%) and Esophagus (5%) have the least osteophilic properties for bone (Phanphaisarn et al, 2016)(Giulio Maccauro et al, 2011). This further evidently illustrated by TN ELumel et al, 2015 from Nigeria in their evaluation of distant metastases in uterine cervical cancer patients showed that only about 19% had bone metastases. This in other words this could mean Kenya would have a low prevalence of spine metastases as compared to other countries.
A step away from the developed countries, (Phanphaisarn et al, 2016) in their analysis of patterns of bone metastases from the common cancers Thailand, they identified the prevalence of bone metastasis as; lung (35.2%), liver (18.8), breast (14.8), cervix (7.8), prostate (6.8) and gastrointestinal tumors (7.8). furthermore they noted that 48.7% of these patients had spine metastases related morbidities that required intervention. The mean age for these metastases was 58.9 years and lung cancer attributive one third of the bone metastases but was mostly in people over 60 years. Metastases secondary to breast, cervix and rectum were commonest in people age below 55 in which case they were mostly women. Overall still women posed the highest risk for spine metastases in the country.
Spine metastases are frequently diagnoses in the posterior portion of the vertebral bodies on plain radiographs in the thoraco-lumber region. The cervical spine is the least affected with at most only about 10% of spine metastases involve the cervical spine. They commonly manifest with pain, neurological deficits, body and or pathological fractures weakness (lee Chong su 2012) (Giulio Maccauro et al, 2011). While evaluating the prevalence and treatment cost of pathological fractures in Taiwan, (Yi-Hu Lee 2011) noticed that most pathological fractures occurred in the vertebrae due to metastatic disease and posed the highest costs treatment on both the patients and hospitals. They estimate that over 10.58 per 100,000 people are hospitalized for spinal pathological fracture. Also (Cho et al, 2015) precisely identified that most pathological fractures occurred at level of T11, L1, L3 and L4 which either way clarifies that most spine metastases are frequently diagnose in the thoraco-lumber region although they further detailed out that over 57.4% had more than four spine metastases at different levels of the vertebrae.
Diagnosis of spine metastases remains a huge diagnostic challenge for most developing countries in Africa and Sub Sahara where two thirds of the radiology diagnostic machines are in Egypt and South Africa. Yet autopsy studies show chances of up to 90% for developing spinal metastases in patients with a history of a malignancy Chong Su Lee 2012. Generally it is estimated that about 20% of patients with spine metastases show neurological deficits and abbu Musubire et al, 2017 in a systemic review of none traumatic spinal cord injuries in resource limited setting note that most of these diagnoses made were either presumptive or based on clinical criteria but even so they note 48% of the non traumatic injuries were rather mainly due to spine metastases (18.6%) or pott’s disease and only 4.6% were secondary to primary tumors of the vertebrae. However the prevalence for spine metastases varied for different sub-Saharan countries, the prevalence was highest in countries with least HIV prevalence. For instance 49% and 28% of non traumatic spinal cord injuries in Cameroon and Zimbabwe were due spine metastases compared to South Africa were pott’s diseases is the commonest cause. In a similar study carried out still at Parienyatwa Hospital in Harare, Zimbabwe Aaron Musara et al, 2016 identified that spine metastases accounted for 22.5% of the non traumatic spinal cord compression cases treated at the hospital.
While evaluating the burden of prostate cancer at the Uganda Cancer Institute M cooneyObuku et al, 2016 reported that of the 182 men with a mean age of 69.5 included in the study, 103 of them (approximately 73%) had bone metastases with the axial skeleton as the commonest site while 30.9% had spinal related neurological deficits and 5.9% had pathological fractures. With regards to this study it is further said that 90% of these men were in stage IV disease most probably because seek diagnosis and treatment late. Considering that Uganda is boarders western Kenya one could therefore infer that the same burden of spine metastases is being incurred not only among Kenyan men with prostate cancer but also among the general population surviving with cancer.
Just to draw more emphasis on my the previous paragraph, John Kamanyu, 2008 no tile in Nairobi Kenya while determining the patterns of bone metastases in breast cancer patients also emphasizes that the vertebrae is the frequent site of metastases. More importantly he notes that about 36.7% of the women with breast cancer had asymptomatic bone metastases hence forth it is very important to always do timely screening for spine metastases in all cancer patients regards of clinical symptoms or stage.
Reference
Takagi T, Katagiri H, Kim Y, et al (2015). Skeletal Metastasis of Unknown Primary Origin at the Initial Visit: A Retrospective Analysis of 286 Cases. PLoS One, 10, 129428.

Cancer pain in Spine metastases and its prevalence
In the previous subtopic we have discussed the patterns and frequency of spine metastases and more precisely we have noticed that the number of cancer patients surviving globally has tremendously increased which consequently means more patients are surviving with devastating painful spine metastases. In this section we shall not only try to have an explicit understanding on the prevalence of spine metastases pain but we shall also dwell into a detailed comprehension of the impact of this pain to the quality of life of the patients, its mechanism and recommend treatment approach. In the subsequent section then we shall discuss the management in details.
Cancer pain can have grievous repercussions on the patient’s survival and quality of life since it is usually associated with numerous co-morbidities that it not only physically breaks a patient but also psychologically derange them. It is therefore paramount that cancer pain is critically addressed in a holistic comprehensive cancer care program. Unfortunately this seems not to be the case as globally it is estimated that between 70 to 90% cancer patients suffer different degrees of pain which can even be severe excruciating pain. Williamson et al 2005 Mantly 2015Johan Hauman 2017
Despite enormous studies on bone metastases and cancer related pain, it is appalling that in the past decade prevalence of cancer pain globally among patients did not show any improvement or decrease when it was compared to the preceding 40 years. It is estimated that actually about 39.3% to 55.0% still suffer post treatment intervention related pain while 66.4% to 70% still suffer advanced disease related pain but worse still over 50% to 64% suffer pain at any stage of disease. Johan Hauman 2017, Maria Teresa Greco 2014 In fact as a result one would say that this is consequently due to the numerous barriers to cancer pain management (i.e. poor community engagement, consistent lack of knowledge on cancer pain, lack of opiods, palliative care and lack of a comprehensive integrated health service system) which evident in numerous developing countries. Ondokor 2017 Even though that was the case, it is believed that over 90% of the world’s morphine is consumed in developed countries alone and only less than 1% that is about 0.39mg per capita consumed in the Sub Sahara kimani eta 2017 but nonetheless there is not major significant difference in cancer pain prevalence in the two regions when ondokor 2017 compared.
Actually in order to cub high cancer pain prevalence, huge efforts have been put on increasing global awareness for cancer pain, understanding its mechanisms and generating new effective pain drugs. But despite all the efforts put it, a majority of cancer patients are still surviving with inadequately managed pain. It is therefore argumentative evident that awareness only might not be sufficient but rather it is imperative that patients receive adequate cancer pain treatment. Greco et al 2014 while assessing the quality of cancer pain reports a slight global decrease in prevalence of under treatment from 43% in 2008 to 32% in 2014. Unfortunately the highest frequencies of under treatment were ranked in Africa at about 63.1% followed by Asia were the rate increased to 59.1%. More so patients in the terminal stage of disease were whose pain was commonly under treated with rates between 37.8% and 58.4%. This however contradicts the palliative goals of care which actually emphasize adequate pain control in the terminally ill.
This is also evidently portrayed in a study conducted at Kenyatta National Hospital in Kenya in which Wanjuki John 2012 et al was evaluating the prevalence and management of cancer pain, similarity also stresses the correlation of pain being highly prevalence among those with metastatic disease furthermore and more importantly the study shows how approximately about 65% of the study population received inadequate pain management due to the only a fraction accessed opioids. His findings were evidently in agreement with Greco et al 2014 and Kimani et al 2017. In his discussion he tackles another important aspect of the WHO analgesics Ladder which if properly applied results in adequate pain relief in up to 90% of the patients Johan 2017. But unfortunately 86% of patients with moderate to severe pain were managed per WHO Step 1 recommendations which are basically non opioids analgesics and another 34 % was on self medications. If that is the case, it is therefore important that an evaluation of the effectiveness of the treatment modalities on cancer pain control be made. Since it remain exclusively challenging to correctly treat pain in patients with specific cancers with pain medications alone incase such pain medicines are contraindicated due to renal or liver impairment. Johan Hauman 2017 This forms a key objective of this study which will be discussed in details in the subsequent subtopic.
In order adequately manage spine metastases pain, it is important to first have a concise comprehension of the mechanism of this pain and its clinical manifestation. Cancer cells commonly metastasize to the spine through four common pathways that usually involve the aterial, lympathatic and venous pathways and or less often through direct invasion of the spine by the primary tumor. Of these cancerous cells frequently spread as an embolus in the venous pathway since they can easily penetrate the natural bone barrier this way. The cancerous cells often lodge in the thorac-lumber region and slowly start to demineralize the vertebrae. Usually this is a slow progressive process before symptoms start to manifest this is usually why more that 36% of the patients usually have asymptomatic spine metastases and why over 75% of spine metastases are diagnose on autopsy in people who had prior history of malignancy.
Currently it is estimated that over 18000 people per year develop symptomatic spinal metastases and it is at this time of manifestation that people usually get diagnosed with spine metastases sometimes when is often too late for curative therapy. Frequently the spine metastases will cause pain, spinal instability, body weakness and neurological deficits with or with urine or fecal incontinence. Pain is usually the first and predominant symptom which can either be localized to a particular spine region or radicular in nature.
Clinically a patient with spine metastases will present with a dull progressive constant back or neck pain that is worse at night and depending on the location of the metastases neurological sensory or motor deficits may occur in weeks or months. Metastases to the lumber pose the highest risk of occurrence of neurological deficits that usually take days to weeks unlike cervico-thoracic metastases that take about weeks to months prior to the initial presentation of pain. It is therefore important that a high suspicion for spine metastases be made for an elderly patient presenting with a long standing history of paraparesis with subsequent inability to ambulate or sensory disturbances. It is estimated that up to 20% of all patients with spine metastases will develop cord compression……
To effectively treat pain, it is very important to understand the cause and type of pain therefore treatment should be pain receptor specific. Broadly pain can be classified as Neuropathic which is usually due to damage to the sensory nervous system or Nociceptive pain which is as a result to of damage to non-neural tissue. Unlike Nociceptive pain that responses effectively to opioids, neuropathic pain on the other hand often have a sub optimal response to opioids but rather response effectively to adjuvant analgesics such as anti convulsants and anti depressants. On that same note it is approximated that about 31.4% of cancer patients suffer from neuropathic pain while another 44.2% have a mixed type of pain Jonan Huaman 2017 WHO 2012. Hence that is why it is vital to understand the type and mechanism of cancer pain before prescribing any treatment.
The pathophysiology of this pain is said to be due to increase in intraosseous pressure of vertebral bodies as a result of cellular invasion by cancellous bone produced by bone destroying osteoclasts which subsequently leads to bone reasorbption and formation of a highly acidic pit within the bone that builds up intraosseous pressure within the endosteum to cause pain or compression of surrounding nerve roots or fibers. Stimulation of endosteal nerve endings results in destruction of bone tissue and release of chemical agents such as prostaglandins, bradykinin, substance P, and histamine which distort the periosteum; the increased stretch of the periosteum by enlarging tumors subsequently leads to pathological fractures or veterbral collapse, the growing tumor can also invade surrounding tissues to cause muscle spasms or inflammatory reactions or compress on a nerve to stimulate expression of neuropeptides which are very sensitive to any noxious stimuli. Milgrom 2017, Chiara D’antonio 2014, Patrick Bone Cancer

Cancer treatment Modalities and their Effectiveness on painful Spinal Metastases

It is absurd that even today many patients with spine metastases are diagnosed or seek medical attention late and more so still a number of those who start treatment early also eventually develop spine metastases. Metastases usually mark the advanced stage of disease where curative treatment is no longer an option. The goal of treatment at this stage is that of palliative care which aims at symptomatic control, pain relief and restoration of neurological function to improve quality of life and survival. Spine metastases are ideally managed with at least one treatment modality i.e. irradiation, surgery, bisphosphonates and sometimes systemic chemotherapy or hormonal therapy. However initial assessments of patient’s performance status, systemic burden of disease, and systemic treatment options are crucial in the management of patients with spinal metastases. Numerous metastatic spine lesion classification systems (Frankel, Harrington, Tokuhashi, Tomita etc) are very helpful in determining the prognosis and life expectancy of these patients which provide a basis for which appropriate treatment modality to use. Radiotherapy is usually preferred to surgery for patients with a life expectancy of less than 6 months.

Radiotherapy
Convectional External Beam Spine Radiotherapy is the cardinal treatment of choice for patients with uncomplicated painful spinal metastases associated with minimal or no neurological deficits, poor prognosis and very short life expectancy. Although it may not be of much benefit in reversing motor impairment due to spinal compression or non radio-responsive tumors, radiotherapy has proved to be of great benefit in cancer induced bone pain control, decreasing tumor size, slowing down its growth thus is crucial in preventing pathological fractures or spinal cord compression. This is so because of the capability of RT to aid ossification, diminish oseoclasts activation, kill tumor cells The EBRT is usually prescribed as single fraction or mulitple fraction but numerous studies have shown regardless of the model used, they are both equally efficient in controlling cancer induced bone pain although single fraction is associated with higher incidence of retreatment at the same painful site. Partial to optimal pain relief within 4 weeks and reduced analgesics use can achieve 50 – 80% patients on EBRT alone. On average EBRT provide pain relief up to at 19 weeks. Comparative studies assessing efficacy of EBRT have actually shown profound benefits of using EBRT alone over laminectomy without stabilization. And that surgery for spinal metastases has been associated with numerous debilitating complications in about 20 – 30% if initial patient assessment is not thoroughly done compared to radiotherapy which is seldom associated with any serious complications. Usually acute complications of RT are self limiting but include pain flares, nausea and vomiting. Another study recommended that 20Gy in 5 multiple fractions was more effective than standard analgesic neuropathic pain. Furthermore some malignancies e.g. ca. prostate demonstrate prospectively close cancer induced bone pain relief if bisphosphonates are compared with EBRT.

Recent advances of highly conformal promising RT modalities like Stereotactic body radiation therapy that deliver high focused doses to targeted vertebrae. Stereotactic body radiation therapy provides a more efficient pain relief of up to 90% with longer remission after 6 months and fewer side effects if compared to EBRT. One limitation of SBRT is that its safety is not well documented and is quite very costly.

Surgery
Historically decompressive laminectomy without stabilization was considered for patients with non radio-responsive large tumor mass despite optimal treatment. However the operation had more undesirable outcome and complications compared to radiotherapy, as a result the number of patients undergoing surgery drastically dropped. That radiotherapy was considered the primary treatment of choice for spinal metastases. Unfortunately patients continued to have suboptimal pain relief, recurrent chronic pain and progressive non reversible motor impairments which radiotherapy alone could not effectively address. But with recent major evolutions in surgical techniques and instrumentation better less invasive approaches like circumferential decompression with ventral tumor resection and spine stabilization have had a tremendous positive impact in improving the quality of life of spinal mets cancer patients. Currently surgery with adjunct radiotherapy is considered to be the primary choice in patients with spinal epidural compression with rapidly progressive motor impairment. Numerous studies have shown surgery to have an added advantage over radiotherapy in restoring functional status and pain relief. In a review on current management of spine mets Jared et al 2017 quoted one study that assessed post ambulatory status in non ambulatory patients before treatment. It was noted that over
62% in the sur¬gery group regained the ability to ambulate versus 19% in the radiation only group. And overall surgery provides longer durations of pain relief and restoration of function in over 90% of patients with spinal mets. Even though surgery might seem to apparently have some superiority in cancer induced bone pain over radiotherapy, no study has firmly concluded so since according to my literature review no prospective study has solely compared pain as an outcome in patients who review surgery or RT. One limitation could be that only less than 2% considered for surgery due to pain as an indication. Therefore numerous studies fail to draw conclusive inference on the population. While many with motor impairment are usually in advanced stage, poor performance status and have short life expectancy to be considered for surgery. On the other hand surgery poses a higher complications risk rate unlike radiotherapy which causes selection bias among surgeons when considering people for surgery. It is therefore my belief that many patients with suboptimal pain relief can optimally benefit from surgery if appropriately selected. But to aid this it is very important that an assessment focusing mainly on pain outcome be done comparing surgery with other treatment modalities.
Other non invasive surgical treatments modalities of spinal metastases for example kyphoplasty and vertebroplasty can be indicated for unstable spine metastases that are either with minimal epidural cord compression or vertebrae instability. Both procedures are equally effective in providing quick pain relief and reduction of reliance analgesics medications in patients with spine mets with or with pathological fractures.

Chemotherapy

Chapter three Methodology
Study Site
This study will be conducted at Moi Teaching and Referral Hospital located in Eldoret Town in Uasin Gishu County situated in western Kenya. It is located 300km North West of Nairobi the capital city of Kenya. MTRH has a bed capacity of 1000 and it is the second largest national referral Hospital after Kenyatta National Hospital. Its catchment is mainly the western part of Kenya and surrounding counties. It also a few receives patients from the Eastern parts of Uganda and other neighboring countries. MTRH has an average outpatient of 210,000 per year which is approximated to about 600 outpatients per day. It also has a cumulative 35,000 inpatients per year and on average about 671 cancer cases were diagnosed annually at MTRH and it serves as the largest cancer treatment centre in western Kenyan. Therefore MTRH is an appropriate site for this study.
Study Design
Owing to the limitations in funds and time, this will be a comparative cross sectional study which will aim at evaluating at cancer induced bone pain. Cancer patients with spine metastases will be purposively selected, enrolled and interviewed at one point in time to assess and compare their pre and post treatment pain outcomes. No subsequent follow up will be done. I would then evaluate the effectiveness of each cancer treatment modality on pain outcome.
Target population
The study will target adult cancer patients with spine metastases who receive treatment at MTRH.
Inclusion criteria
Exclusion Criteria