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Introduction

Table of Contents
1 Cancer in Canada
2 Using This Oncology Handbook
3 Systemic Therapy (Chemotherapy and Targeted Therapy)
        3.1 Chemotherapy
        3.2 Targeted Therapy
        3.3 Radation Therapy
        3.4 Cancer Screening
        3.5 Oncologic Emergency

Cancer in Canada

    Cancer is the leading cause of death in Canada (29.9%). A diagnosis of cancer is devastating, not just to the person receiving the diagnosis, but to the family and friends, as unfortunately some patients may die of their disease. Improvements in cancer treatments (excluding lung cancer) has resulted in survival of more than 75% of patients at five years.

    Two in five Canadians will develop cancer in their lifetime, and unfortunately 1 in 4 will die of cancer. According to the Canadian Cancer Society, it is estimated that 191,300 Canadians will develop cancer, and 76,600 will die of cancer in a year. More than half of new cancer cases (52%) will be lung, breast, colorectal and prostate cancer. Lung cancer is the leading cause of cancer death, causing more cancer deaths among Canadians than the other three major cancer types combined. Despite this large impact on mortality by lung cancer, there has been a substantial drop in the lung cancer death rate (especially for men) over the past 25 years, which has driven a decline in the overall cancer death rate.

    Overall, the five-year relative survival ratio for people diagnosed with cancer is 63%, but it ranges widely by the type of cancer. Some cancers have very high five-year relative survival ratios, such as thyroid cancer (98%) and pancreatic cancers (8%) have consistently low five-year relative survival ratios. Canadian cancer statistics report 810,045 survivors affected by cancer. Most cancer survivors lead productive lives, however some need to be supported to control side effects of treatment or have psychosocial needs during and after completion of treatment. The goal is to improve survival, develop better overall care for those with cancer and reduce incidence of cancer by primary and secondary prevention. The four most common cancers in Canada—breast, prostate, colorectal and lung—comprise more than half of all cancers diagnosed (Table 1).

Table 1. Most Common Cancers in Canada, Canadian Cancer Statistics, 2014

   Disease Site
Incidence
Mortality
Male
Female
Male
Female
   Prostate
23,600
0
4,000
0
   Lung
13,400
12,700
10,800
9,700
   Breast
210
24,400
60
5,000
   Colorectal
13,500
10,800
5,100
4,200
   Subtotal
50,710
47,900
19,960
18,900
   All
97,700
93,600
40,000
36,600

    Cancer treatments are multidisciplinary and complex, which results in a difficult journey for patients and their families, and they need compassion, support, and education to cope with their cancer diagnosis and treatments. Treatments depend on the type of cancer, stage of the disease and performance status of the patient. In oncology, performance status is an attempt to quantify a cancer patient’s general well-being. This measure is used to determine whether a patient can receive chemotherapy, whether dose adjustment is necessary, and used as a measure for the required intensity of palliative care. It is also used in randomized controlled trials in oncology as a measure of quality of life. See page 167 for scales of ECOG, Karnofsky and WHO to assess performance status (PS).

    Cancer treatments are multidisciplinary and at SMH cases are reviewed in the tumour boards that are held weekly (Breast and GI) or biweekly (Lung, GU, Gynae). The participants are the pathologists, surgeons, oncologists and radiation oncologists, who meet for pathology review and plan management.

    Early stage cancer is treated with surgery and systemic therapy, in areas such as breast, colon, lung, etc. Systemic therapy can be given prior to surgery or radiation (neoadjuvant) when dealing with advanced breast, head and neck, and rectal cancers, to reduce the size of the tumour and make curative surgery possible. Systemic treatments after surgery (adjuvant) are given for 4-12 cycles to prevent recurrence in breast, colon, lung and other cancers.

    Goals of cancer treatment can be curative or palliative. Systemic chemotherapy can be curative in some advanced cancers such as Hodgkin lymphoma, testicular cancer, and leukemia etc. Palliative systemic therapy is given to control the disease and prolong survival, with a good quality of life. Palliative treatments are continued until progression of disease or toxicity.

    Radiation treatment is used in early stage cancer with curative intent (i.e. to prevent local recurrence) and to avoid mutilating surgery, as in locally advanced breast, sarcomas, head and neck, and rectal cancers. Radiation treatment with palliative intent (control symptoms) is given for unresectable non-small cell lung cancer (NSCLC) and for metastases to bones, brain, liver, and lung.

    All cancer patients should be encouraged to participate in clinical trials to improve care, as well to improve treatment for cancer patients. Patients with metastatic disease should be referred for testing (COMPACT trial at Princess Margaret Hospital) for mutations and to assess the tissue of the patients for eligibility of targeted therapy, i.e. personalized medicine. At present, this is being done as a clinical trial and hopefully personalized medicine will be available to all patients with early stage and metastatic disease.


Using This Oncology Handbook

    This Oncology Handbook and website was developed in 2011 for undergraduate medical students and post graduate trainee students rotating through oncology. This handbook and and web-based tool was implemented and evaluated after REB approval in 2012. Thirty three trainees while on oncology rotation were evaluated by pre and post test questionnaires. This study was completed in 2014. The results showed statistically significant improvement in knowledge on post test scores. In the second edition, we have updated the information and added a few more sections.

    Its purpose is to provide comprehensive information on staging and management of common cancers, as well as outlining the basic curriculum of oncology education. This handbook outlines the diagnosis of cancer, including staging investigations, which is a vital component for prognosis and planning of treatments.

    To simplify this handbook, each section of common malignancies is presented in the same format. First, a brief disease overview is provided, followed by a discussion of treatment modalities, and finally, an outline of follow-up care. In the disease overview for common cancers, practical and clinically relevant information is summarized under Risk Factors, Prevention, Screening, History, Examination, Staging Investigations, AJCC Cancer Staging, Prognosis, Management (adjuvant and metastatic treatment options) and Follow-up guidelines.

    An understanding of the patient’s personal and family history (with a focus on relatives who have had cancer, the type of cancer and at what age), and current physical condition is an important initial step in the management of cancer patients. Detailed information as part of the best possible medication history (BPMH), including over-the-counter and prescription medication, is important to avoid drug interactions. A large number of cancer patients are using complimentary medications (such herbal and holistic remedies), which should also be noted when taking down a patient’s medical history.

    For geriatric patients (75 or over) a focused geriatric history or comprehensive geriatric assessment should be done to assess fitness, vulnerable and frailty of patients. Impact of geriatric assessment in oncology is significant and evidence shows that they identify deficits not detected in standard history and physical examinations. It helps us optimize non-oncologic domains, detect geriatric variables with prognostic significance, change chemotherapy treatment intensity and finally improves tolerance to chemotherapy. Geriatric risk stratification screening or comprehensive geriatric assessment to assess functional status, fatigue, comorbidity, cognition, mental health, social support, nutrition, poly-pharmacy, geriatric syndromes (SIOG recommendation 2015. Ann Oncology 2015; 26;288-300.)

    See performance status section for references and bedside tests.

    A detailed, oncology-focused physical examination includes lymph node palpation and evaluation of common sites of metastases.

    For details regarding chemotherapy regimens, please refer to: www.cancercare.on.ca

Systemic Therapy of Cancer

    Medical Oncology is a sub-specialty which deals with systemic therapy of cancer. The goal is optimal management of cancer with minimal short and long term toxicity. Cancer treatments are multimodal (i.e. surgery, radiation and chemotherapy, biologics and targeted therapy) and patients need to be supported and triaged through this complex system.

    Standard treatments used in the clinics have gone through clinical trials, with phase I to asses toxicity, phase II to assess efficacy, and phase III to compare standard treatment to experimental treatment. The section on pivotal trials in this handbook provides references to practice changing treatment trials, and additional references to abstracts can be found on the website.

Chemotherapy

    Chemotherapy is the broad term referring to the use of chemicals/drugs to treat cancer. It includes cytotoxic agents that target rapidly dividing cancer cells or cancer cells that over-express specific genes and receptors. Chemotherapy agents are commonly classified by their mechanism of action or source.

Alkylating Agents

    Alkylating agents cause DNA strand breaks in cells by covalent bonding of the alkyl group to cellular nucleophilic sites. Their actions are not selective for cancer cells and may cause acute and delayed toxicities to other tissues.

    Non-classical alkylating agents act through a similar mechanism of action as alkylating agents but they do not have the classic alkylating chloroethyl group.

Antimetabolites

    Antimetabolites are structurally related to naturally occurring compounds involved in cellular production. There are pyrimidine and purine analogues.

Folate Antagonists

    Folate antagonists inhibit the availability of cellular folate, which is an essential cofactor in many DNA synthesis reactions.

Anti-tumour Antibiotics

    Anti-tumour antibiotics cause direct DNA damage or cell apoptosis by DNA transcription and duplication.

Antimicrotubule Agents

    Antimicrotubule agents target microtubules which play an important role in mitosis and in the maintenance of cell shape, scaffolding, and function. There are two types: vinca alkaloids and taxanes. Vinca alkaloids interact with tubulin and disrupt microtubule assembly, ultimately inducing metaphase phase arrest in dividing cells. Taxanes stabilize microtubules against depolymerisation which prevents disassembly and ultimately inhibits the dynamic reorganization of the microtubule network.

Topoisomerase Inhibitors

    Topoisomerase inhibitors act against DNA topoisomerases, which are key enzymes required for DNA replication. They relax the torsional stress that occurs during the unwinding of DNA double helix during cell division, relax supercoiled DNA, and decatenate intertwined DNA strands.

Classification of Cytotoxic Agents

Alkylating Agents Anti-metabolites Microtubule Inhibitors Anti-tumour Antibiotics Topoisomerase Inhibitor
Cyclophosphamide
5-Fluorouracil
Vincristine
Anthracyclines
Irinotecan
Ifosphamide
Capecitabine
Vindesine
Daunorubicin
Topotecan
Carboplatin
Gemcitabine
Vinblastine
Doxorubicin
Cisplatin
Methotrexate
Taxanes
Epirubicin
Chlorambucil
Mercaptopurine Cytosine
Paclitaxel
Mitoxantrone
Melphalan
Arabinoside
Docetaxel
Bleomycin
Carmustine
Vinca Alkaloids
Oxaliplatin
Temzolamide
Pemetrexed

    Chemotherapy dose is commonly calculated according to the body surface area (mg/m²), but may also be weight-based (mg/kg) or fixed. In Ontario, the preferred formula is the Mosteller equation to avoid transposition errors with height and weight.

    For calculation, refer to: www.halls.md/body-surface-area/bsa.htm.


Common Chemotherapy Regiments Used in Clinics

Abbreviations:
CMF: Cyclophosphamide, methotrexate,5- fluorouracil
AC: Doxorubicin (adriamycin), cyclophosphamide
TC: Docetaxel (taxotere),cyclophosphamide
FAC: 5-Fluorouracil,doxorubicin , cyclophosphamide
TAC: Docetaxel, doxorubicin, cyclophosphamide
FEC-D: 5-Fluorouracil, epirubicin, cyclophosphamide, followed by docetaxel
Folfox: Folinic Acid (Leucovorin), 5-fluorouracil, oxaliplatin
Xelox: Capecitabine (Xeloda,) oxaliplatin
Folfiri: Folinic Acid (Leucovorin), 5-fluorouracil, irinotecan
GemCis: Gemcitibine, cisplatin
VinoCis: Navelbine(Vinorelbine), cisplatin
BEP: Bleomycin, etoposide, cisplatin (Platinum)
ABVD: Doxorubicin, Bleomycin, Vinblastine and Dacarbazine
R-CHOP: Rituxamab, cyclophosphamide, doxorubicin, vincristine, prednisone
TaxolCarbo: Paclitaxel, carboplatin

For information on chemotherapy regimens for cancer type, refer to Cancer Care Ontario’s Drug Formulary website: www.cancercare.on.ca/toolbox/drugformulary

Toxicity of Chemotherapy

    Chemotherapy agents are cytotoxic and target rapidly dividing cells. These include cancer as well as other cells that are naturally dividing in the body, such as hair, nails, mucosa, etc.

    Myelosuppression is a common side effect of many chemotherapy agents. In most, the lowest or the nadir counts typically occurs around day 7 - 10, and counts recover within 3-4 weeks. However, some chemotherapy agents have long lasting myelosuppression and the nadir counts are at 2-4 weeks and recovery takes almost 6 weeks. The most common complication of myelosuppression is neutropenia leading to febrile neutropenia, which is an oncologic emergency for which empiric antibiotic treatment is required urgently. Growth factor support is used to prevent life threatening febrile neutropenia. ASCO guidelines support primary prophylaxsis for regimens with at least a 20% risk of febrile neutropenia.

    Other hematologic complications of chemotherapy is anemia and thrombocytopenia. Risk of venous thromboembolism and prophylaxis should be considered for high-risk patients and need to be individualized. Chemotherapy side effects include: Early or Acute and Chronic or Delayed as in the table. For further details of side effects go to www.cancercare.on.ca.

    The goal is to alleviate short and long-term toxicity with supportive care. Side-effects can be divided into early or late as in the table and most of them can be prevented or treated.

Targeted Therapy

    Targeted cancer therapies are drugs that block the growth and spread of cancer by interfering with specific molecules involved in tumour growth and progression. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than other types of treatment, including chemotherapy and radiotherapy, and less harmful to normal cells. Activation of growth factor receptors such as epidermal growth factor receptor, either by ligand stimulation or receptor overexpression/mutation, is one of the major mechanisms responsible for the upregulation of signal transduction pathways leading to growth and proliferation of cancer cells.

    Targeted cancer therapies interfere with cancer cell division (proliferation) and spread in different ways. Many of these therapies focus on proteins that are involved in cell signaling pathways, which form a complex communication system that governs basic cellular functions and activities, such as cell division, cell movement, how a cell responds to specific external stimuli, and even cell death. By blocking signals that direct cancer cells to grow and divide uncontrollably, targeted cancer therapies can help stop cancer progression and may induce cancer cell death through a process known as apoptosis.

    Targeted therapy is being used in many cancers in combination with chemotherapy to block these pathways. These targeted therapy drugs are either large molecule monoclonal antibodies (MAB), or small molecule tyrosine kinase inhibitors (IB) as shown in the table below.

    Toxicity of targeted therapy is different from chemotherapy. Common side effects are allergic/anaphylactic reactions and usually prevented with dexamethasone; skin rashes; and increased risk of cardiotoxicity as in trastuzumab and bevacizumab.

Management of Skin Reactions

    Mild rash: Generally localized papulopustular reaction, minimal symptoms, no impact on ADL, no sign of superinfection

  • Management: Continue EGFR inhibitor at the current dose and monitor for change in severity, no treatment OR topical steroids or topical antibiotics. Reassess after 2 weeks; if reactions worsen or do not improve, manage as moderate rash and use of topical steroids.

    Severe rash: Generalized papulopustular reaction, severe symptoms (eg, pruritis, tenderness), significant impact on ADL, potential for superinfection

  • Management: Interventions for severe rash include: Reduce or discontinue EGFR inhibitor dose as per label and monitor for change in severity; continue treatment of skin reaction with the following: topical steroids, topical antibiotics, or topical immunomodulators PLUS oral antibiotics PLUS oral steroids. Reassess after 2 weeks; if reactions worsen, dose interruption or discontinuation may be necessary.

Immunotherapy

    Immunotherapy, such as inhibitors of CTLA4, PD1 and PDL1 as an important modality in management of melanoma and in lung cancer and recently exciting results in other solid tumours. Patients need to participate in immunotherapy trials. Findings from four clinical trials released at the American Society of Clinical Oncology’s (ASCO) 51st Annual Meeting show a promising new role for immunotherapy in patients with a wide range of solid tumors. The new study results demonstrate the effectiveness of immunotherapy drugs targeting the PD-1 protein in advanced liver, head and neck, lung, and colorectal cancers. Several of the studies also identified genomic markers that can be used to determine which patients stand to benefit most from these new therapies. The field of targeted immunotherapy gets more exciting every year. With these trials, we’re rapidly moving past the era in which immunotherapies are seen as breakthroughs for melanoma alone. Remarkably, these drugs are proving effective in other cancers where practically no other treatments work. Just as important, it’s possible that we’ll be able to pinpoint, in advance, which patients are the best candidates for these therapies.

Studies presented include:

  • A phase II study reports that a specific genomic abnormality called mismatch repair (MMR) deficiency predicts response to the anti-PD-1 antibody pembrolizumab. This marker predicted responses in patients with colorectal, endometrial and several other types of cancer.
  • A phase I/II study identified a potential new role for nivolumab in advanced liver cancer – a disease where just one FDA-approved treatment exists. Approximately one in five patients responded to this immunotherapy.
  • A new study identifies a promising role for the anti-PD-1 antibody pembrolizumab in patients with head and neck cancer. One in four patients responded to pembrolizumab, irrespective of PD-L1 biomarker status.
  • A randomized phase III study establishes nivolumab as a possible standard second-line treatment option for non-squamous non-small cell lung cancer. Patients treated with nivolumab were more likely to respond, lived longer and saw fewer side effects than those treated with standard docetaxel chemotherapy – especially those with high PD-L1 levels.

Side-effects profile is different than chemotherapy and is immune related and manageable pancreatitis, pneumonitis, endocrine disorders, rash/pruritis and thrombocytopenia.

Radiation Therapy

    Radiation therapy is the use of high energy radiation to kill cancer cells and shrink tumours. It is the most commonly used method of cancer treatment and is recommended for many types of cancer. Radiation therapy can be used alone or in conjunction with surgery and/or chemotherapy (adjuvant or neoadjuvant).

    For certain types of cancer, radiation is the only treatment required. Radiation treatment may also be used to provide temporary relief of symptoms or to treat malignancies that cannot be removed by surgery as in lung cancer.

    Because radiation is most harmful to rapidly growing cells, radiation therapy damages cancer cells more than normal cells. Specifically, radiation therapy damages the DNA of cancer cells. Doing so prevents the cancer cells from growing and dividing. Certain healthy cells can also be killed by this process and thus, radiation therapy can also lead to some side effects.

    Side effects vary among treatment plans and site of radiation. However, the most common side effects experienced during radiation therapy are fatigue, changes of the skin and rarely sarcoma. One of the side-effects of surgery and radiation is lymphedema as in breast cancer.

Symptom Management and Supportive Care

    Over the last decade, a significant amount of effort is placed on the alleviation of acute and long-term side effects resulting from anti-cancer therapy.

    Acute side effects are nausea and vomiting, mucositis and esophagitis, anorexia and cachexia, diarrhea, fatigue, skin rashes, venous thrombosis and life threatening febrile neutropenia. Taxanes can cause allergic reactions due to the preservative and requiresteroid prophylaxis. Thus, patients need support and education on how to manage these side effects during chemotherapy.

    Since the use of 5-HT3 antagonists (ondansetron, granisetron) to prevent nausea and vomiting, highly emetogenic chemotherapy can be delivered in the outpatient setting, and this has led to improved quality of life and less hospitalization. NK inhibitors (Emend) can be used for patients on highly emetogenic chemotherapy. Primary prophylaxisis with growth factors (G-CSF) to prevent life-threatening febrile neutropenia. Side effects can vary in each individual patient and need to be counselled accordingly.

    Long-term toxicity from treatment may be cardiotoxicity, neuropathy, cognitive dysfunction, reproductive dysfunction, osteoporosis, etc, and need to be prevented, recognized, and managed in cancer survivors. Secondary malignancy can result from cancer therapy such as breast cancer in young women treated with mantle radiation for Hodgkins lymphoma. Patients who receive radiation to the neck should be evaluated for hypothyroidism. A rare side effect of radiation is sarcoma. Chemotherapy can rarely cause secondary malignancies such as, acute myeloid leukemia. Tamoxifen can rarely cause uterine cancer.

    Patients undergoing treatments for cancer may experience not only physical, but also psychosocial problems, which need to be addressed promptly by the oncology team to improve cancer care.

Survivorship and Follow-up Care

    With early diagnosis and improved treatments, the number of cancer survivors have increased, with breast cancer being the largest group of survivors. The American Cancer Society estimated 13 million cancer survivors in USA and 810,045 in Canada in 2014. Cancer survivorship is defined from the time of diagnosis through the remaining years of life – the period following first diagnosis and treatment, and prior to the development of a recurrence of cancer or death. Family members, friends and caregivers are also impacted by the survivorship experience (from Cancer Patient to Cancer Survivor, Institute of Medicine, USA, 2006).

    The challenge is that cancer treatments are complex and multimodal, with short and long term toxicity, and patients need follow-up and coordinated care by the primary care providers and the oncologist. Goals of follow-up is early identification and management of treatment related complications, and other comorbid conditions. It is also important for recognition and treatment of recurrences or a second primary, and early referral to the oncology team. Primary care providers need a better understanding of the cancer-related toxicities. These challenges and experiences are different for each individual cancer survivor. Cancer care is not ‘one-size-fits-all’; it should be personalized and patient centered. Although the majority of cancer survivors lead very productive lives, all domains of health should be addressed when these individuals are seen. Cancer in some instances behaves like a chronic disease – a shared care model may work, but coordination of care or planning of care is essential between the health care professionals.

    The difficulties faced by survivors may relate to self-image, fear of recurrence, toxicity, depression, relationships, job security, among other concerns (ASCO, 2014). To improve the patient's experience along every step of this journey, we have to palliate symptoms, prevent recurrences and/or new cancers, and improve overall well-being. Physicians caring for cancer survivors should be aware of the physical, psychosocial, emotional, and spiritual effects resulting from diagnosis and treatments of cancer. With education and support, the majority of survivors reintegrate into the community as highly functional individuals.

    Communication is required between oncologists, patients, and family practitioners to improve all aspects of cancer care, and management of other associated chronic conditions such as hypertension, coronary artery disease, and diabetes. We need to encourage patients to cease smoking, maintain a healthy lifestyle (BMI less than or equal to 27), reduce alcohol intake to less than three glasses of wine a week or equivalent, participate in moderate exercise (brisk walking at least three times weekly), maintain a healthy diet (five servings of vegetables daily), and reduce stress (with practices such as meditation, yoga, Tai-Chi, and pilates). Integrative oncology services, such as acupuncture for pain control, have shown benefit in helping cancer patients during treatment (ASCO 2014).

    For information about breast cancer survivors, refer to Survivorship Guide (http://breastcancer09.utorontoeit.com/Home.html)

Palliative and End-of-Life Care

    Unfortunately, many cancer patients develop recurrence or receive treatments to control disease for palliation. During this difficult time, they require ongoing support services as needed. There is data that supportive care improves survival in advanced non-small cell lung cancer (Yoong et al., 2013). Early palliative referrals and goals of care discussion improve quality of life and help patients through this difficult journey.

    The goal of end-of-life care after discontinuation of active anti-cancer therapy shift from cure and survival to the optimization of physical comfort, psychosocial well-being, and quality of life and support of the family members. This phase of care focuses on the alleviation of physical symptoms, cognitive impact, and psychosocial concerns, which may diminish the patient’s quality of life. How to address these difficult issues for cancer patients remains a challenge and is an art that can be mastered with techniques on caring, that are also patient centered, as each patient can be very different. Furthermore, it is important to discuss end-of-life issues with patients, such as “do not resuscitate” order, comfort measures only from active treatment, and transfer to palliative care unit or hospice, etc.

    Baile, Buckmanet al.(2000) developed the SPIKES model, which is a “six step protocol for delivering bad news” for patients with cancer.


Cancer Prevention and Screening

    Prevention strategies for cancer include smoking cessation, preventing obesity, reducing sun exposure, exercising, maintaining a healthy lifestyle, and reducing alcohol intake. (Refer to www.cancer.ca for more prevention strategies.) Screening tests can help find cancer at an early stage, before symptoms appear. When cancer is diagnosed early, it may be easier to treat or cure. By the time symptoms appear, the cancer may have grown and metastasized. This can make the cancer harder to treat or cure. We have summarized the screening recommendation for asymptomatic subjects with normal risk. Cancer patients are also at risk of second primary and should follow these guidelines.

*These recommendations were made for the general population—asymptomatic people who have no risk factors, other than age or gender, for the targeted condition.

Source: Modified from ASCO SEP second edition 2010


Cancer of Unknown Primary Site (CUPs)

Disease Overview

    Cancer of unknown primary site (CUPs) represent a heterogeneous group of metastatic tumours for which a diagnostic work-up fails to identify the site of origin at the time of diagnosis. CUPs account for 3–5% of all malignancies. CUPs presents with metastatic cancers and the prognosis for most patients with CUPs is poor. However, appropriate diagnostic work-up can identify a group of CUPs patients who can benefit substantially from specific therapy. It is important to avoid exhaustive investigations in CUPs and diagnose the types of cancer that are treatable, and if in good performance status, treat with a trial of palliative empiric therapy with gemcitabine and cisplatin.

Diagnostic and Staging Guidelines for CUPs

Pathology

    Diagnosis of CUPs requires an excisional biopsy and a proper pathologic evaluation with immunostaining, and geneprofiling is experimental. Patients can be referred for specific mutations on the COMPACT trial at UHN.

These tumours are categorized into:

  1. Well differentiated and moderately differentiated adenocarcinoma (60%)
  2. Squamous cell carcinoma (5-10%)
  3. Undifferentiated neoplasms (35%)
  4. Poorly differentiated carcinomas, including poorly differentiated adenocarcinoma (immunostains can help to differentiate between sarcoma, melanoma, lymphoma, germ cell, and carcinoma)

    Immunohistochemistry is used by the pathologist to identify tissue of origin and exclude lymphoma (CD 45, CD57, CD20), germ cell tumours (BHCG) which are curable with appropriate treatments. Cytokeratin stains epithelial tumours such as CK 20+, CK7- for colorectal cancer, CK 7+ CK20- for lung, breast etc. Thyroid transcription factor (TTF) stains for thyroid cancer and lung cancer. Other stains are S100 for melanoma, vimentin for sarcoma and NSE, chromogranin and synaptophysin for neuroendocrine tumours.

    An algorithm for the practical management of patients with CUP, including recognition of specific subsets, exclusion of non-CUP neoplasms and use of prognostic parameters in the clinical practice, is summarized. Therapy should be tailored on an individual basis according to the clinicopathological subset of distindct prognosis. Patients can be started on empiric therapy with gemcitabine and cisplatin and monitored closely to see improvement in quality of life and symptoms and performance status.

Oncologic Emergency

When a patient presents with an oncologic emergency, urgent diagnosis and management is required.

There are many types of oncologic emergencies, which can be an acute life threatening event at presentation or during the course of the illness; it could be related to cancer (spinal cord compression), its treatment (febrile neutropenia), or unrelated to cancer (pulmonary embolus).

Factors that Influence the approach to an oncologic emergency depends on:

  • General condition of the patient – end stage/undiagnosed cancer/reversibility
  • Duration
  • Type and stage of cancer
  • Treatment options
  • Patient's and Family's desire

Patients should be counseled about acute problems during treatments such as sudden onset of shortness of breath, leg swelling, and febrile neutropenia, etc.

Oncologic emergencies can be:

Mechanical

  • Spinal Cord Compression (need urgent dx and referral to neurosx or radiation)
  • Superior Vena Cava Syndrome (need dx and treatment according to type of cancer)
  • Cardiac Tamponade

Metabolic

  • Tumour Lysis Syndrome
  • Hypercalcemia
  • Cardiac Tamponade

Chemotherapy-related

  • Febrile neutropenia
  • Chemotherapy induced diarrhea

Hematologic

  • Deep venous thrombosis
  • Pulmonary embolus

For further details, see our Oncologic Emergencies section.