Kaposi’s Sarcoma

Clinical Description

Kaposi sarcoma (KS) is an indolent angio-proliferative spindle-cell tumour derived from endothelial and immune cells infected with human herpes virus type 8 (HHV-8); also known as Kaposi sarcoma herpes virus (KSHV)). KS is currently the most common cancer in Malawi.

Signs and Symptoms

• KS presents as mucocutaneous and visceral lesions.
• Mucocutaneous lesions usually manifest as dark, red, purple, or brown papules, plaques, nodules, cauliflower lesions, with or without edema on the skin or mucous membranes. The lesions may ulcerate and form a whitish creamy layer of necrotic tissue.
• Visceral disease occurs in organs such as lungs or GIT and may cause effusions in serous body cavities.
• KS can co-exist with other Human Herpes Virus 8 associated conditions such as

Castleman’s disease and Primary Effusion Lymphomas.

Investigations

• HIV test if unknown. If positive and on treatment, do CD4, Viral Load to rule out

HAART failure.

• CXR to rule out lung involvement, Gastroscopy and Colonoscopy if GIT related

Signs and Symptoms

• Clinical diagnosis in HIV positive patients only without histology.
• Do a biopsy for histology if clinical picture not typical of KS at presentation or in HIV negative patients.
• HHV8 immunohistochemistry may be a useful addition

Treatment

• Treatment depends on the extent of disease; early stage can be controlled with ART alone.
• All patients with HIV associated KS should receive ART.
• Visceral and T1 disease should be considered for rapid initiation of treatment.
• Local therapies: intralesional treatment, radiation and surgery are local therapies applied to KS lesions in general. Radiation therapy is reserved for disease that is limited but causing severe pain, bleeding, distress or is chemo-refractory. Surgery is reserved for aggressive local KS which is causing severe disfigurement, organ malfunction and overwhelming sepsis. In this case organ amputation is necessary, followed by systemic chemotherapy.
• Systemic therapy: several cytotoxic chemotherapy agents are effective in providing rapid improvement in the majority of patients with locally aggressive and disseminated KS.

PHARMACOLOGICAL THERAPY

First line treatment:

• Paclitaxel 100 mg/m2 2 weekly IV 6 - 8 cycles.
• Always premedicate with Dexamethasone 8-16 mg IV/PO, Cimetidine 400 mg PO, Ondansetron 8 mg IV/PO and Promethazine 12.5 mg IV 30 minutes before to reduce the risk of hypersensitivity reactions.
• If not effective after 4 - 6 cycles, refer to a specialist for further evaluation.

Note: The initial assessment and first line therapy should be done at a health care facility with competent staff in handling cytotoxic drugs and safe drug handling equipment/tools to protect staff have been introduced. The FBC machine should have proper QC/QA to ensure correct counts are used.

CERVICAL CANCER

Clinical Description

• Cervical cancer is the third most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries including Malawi. Human papillomavirus (HPV) infection must be present for cervical cancer to occur.

Signs and Symptoms

• Physical symptoms of cervical cancer may include the following:
• Asymptomatic (diagnosed during routine screening)
• Symptomatic (advanced disease)
• Abnormal vaginal bleeding (In between menstrual cycle, post- menopausal)
• Vaginal discomfort
• Malodorous discharge
• Dysuria
• Early Disease: erosion of cervix or changes of chronic cervicitis
• Late/advanced disease: Ulcerative or fungating cervical lesion on speculum examination

Investigations

• Punch biopsy for histology
• Screening for any woman of reproductive age group above 25 years using VIA, Pap smear or HPV DNA (in research setting for now).
• HIV positive patients are advised to be screened once they reach reproductive age.
• Speculum and cervical punch biopsy for histological analysis.
• Speculum examination before any antibiotic course for women presenting with abnormal vaginal bleeding or foul-smelling discharge.

Treatment

Immunization

• Vaccination with HPV vaccine is recommended in girls between 9 to 14 years.

Surgery

• Fertility sparing (Trachelectomy in stage I cancer).
• Forms of radical hysterectomy with lymph node dissection:
• Wertheim-Meigs
• Wertheim-modification
• Total mesometrial resection.
• Exenteration (for locally advanced disease or pelvic recurrences)

Radiotherapy

• If no LND was done, to be considered for Radiotherapy.
• Radio-chemotherapy plus brachytherapy.
• Palliative radiotherapy if advanced disease.

Pharmacological

• Chemotherapy regimens to be given at TERTIARY hospitals. Neoadjuvant chemotherapy where access to radiotherapy is limited.
• Combination is better than monotherapy
• Paclitaxel, Cisplatin, Fluorouracil, Carboplatin, Bevacizumab are drugs of choice
• Palliative care is critical in providing pain control with morphine (see section on pain control), controlling bleeding, and providing end of life care.
• Consider discussing with Oncology team for palliative chemotherapy in the following patients:
• PV bleeding
• Intractable pain on optimal analgesia
• Symptomatic metastatic disease

Note: Assessment needs to be done at a tertiary institution with close discussions between

Gynae-oncologists, Urologists, Pathologists, Radiologists, Oncologists and Palliative care team to jointly stage and decide on treatment.

BREAST CANCER

Clinical Description

• Breast cancer is the common term for a set of breast tumor subtypes with distinct molecular and cellular origins and clinical behaviour. The most common histology is Ductal Carcinoma. Sarcomas and lymphomas may also affect the breast. Breast cancer can also occur in men.

Signs and Symptoms

Early breast cancers may be asymptomatic, and pain and discomfort are typically not present. If a lump is discovered, the following may indicate the possible presence of breast cancer:

• Change in breast size or shape
• Skin dimpling or skin changes
• Recent nipple inversion or skin change, or nipple abnormalities
• Single-duct discharge, particularly if blood-stained
• Axillary lump

Investigations

• It is advisable for women above age 20 years to do Self Breast Examination (SBE) monthly for potential masses.
• Mammography and breast USS is recommended for women between 50 – 75 years.
• Definitive diagnosis is through histology of the breast mass and ipsilateral axillary lymph nodes. This is more superior to cytology which should be understood as a preliminary diagnostic test.
• Cytology should be considered for suspicious lymph nodes.

Treatment

• Treatment for breast cancer is multimodality.

Non-pharmacological

Surgery

• Modified radical mastectomy and axillary lymph node clearance of level I and II nodes.

Note: Lumpectomy or breast conserving surgery in state hospitals should be reserved until radiotherapy facilities are available.

Pharmacological

Chemotherapy

• This may be given as neo- adjuvant (before surgery) or adjuvant (after surgery). The first option has advantage of down-staging to make difficult to operate tumors resectable. Protocols include:
• TAC, AC +/-Taxane, TC, CMF, FEC-75
• HER 2 +: Add Trastuzumab
• Patients on Doxorubicin or Epirubicin should have cardiac assessments (ECHO) before and during treatment
• For Metastatic disease consideration of chemotherapy for younger patients or Tamoxifen in elderly patients who may not tolerate chemotherapy.

Hormonal treatment:

• If ER/PR positive, Tamoxifen 20mg PO daily +/- Goserelin 3.6mg SC every 28 days or Ovarian Ablation if premenopausal.
• If postmenopausal, consider Anastrazole 1 mg daily PO or Letrozole 2.5 mg PO.

Radiotherapy

• Adjuvant post-surgery to minimize recurrence and improves survival from breast cancer
• Palliation to breast or chest wall for pain, bleeding as well as in brain metastases and bone metastases with or without spinal cord compression
• Bone Disease: Palliation should include Denosumab 60 mg sc 6 monthly or Zoledronic Acid 3.3 to 4 mg 1 to 3 monthly. Pathological fractures should be discussed with Orthopedic team.

OESOPHAGUS CANCER

Clinical Description

• This is a malignant tumor of the esophagus. The risk of cancer of the esophagus is increased by long-term irritation of the esophagus, such as from smoking, heavy alcohol intake, and barrett esophagitis. The most common histological subtype in

Malawi is squamous cell carcinoma.

Signs and Symptoms

• Unexplained dysphagia or odynophagia
• Weight loss

Treatment

Note: All patients who are not fit for above curative options and or have metastatic disease should be considered for:

• Endoscopic stent placement
• Feeding tube
• Palliative chemotherapy
• Palliative Radiotherapy

Pharmacological

• Cisplatin, Fluorouracil, Carboplatin, Paclitaxel, Gemcitabine, Capecitabine are options to choose from +/- Radiotherapy.

PROSTATE CANCER

Clinical Description

• Cancer that occurs in Prostrate. One of the most common Cancer in Men
• Many prostrate cancers grow slowly and are confined to the prostrate gland, where they may not cause serious harm. However, while some types of prostrate cancer grow slowly and may need minimal or even no treatment, other types are aggressive and can spread quickly.
• Prostrate cancers that’s detected earlier, when its still confined to the prostrate gland has the best chance for successful treatment.

Signs and Symptoms

• Prostate Cancer may cause no signs and symptoms in its early stages.
• Prostate cancer that is more advanced may cause signs and symptoms such as
• Trouble Urinating
• Decreased force in the stream of urine
• Blood in the urine
• Blood in semen
• Bone pain
• Weight loss
• Erectile dysfunction

Investigations

• Transrectal ultrasound guided prostate biopsy (12 core biopsy is the standard; 6 from each lobe) and PSA.
• Fusion biopsies are not routinely done in the country now.
• Patients presenting with ‘BPH’ should have a routine prostate biopsy to rule out co- existing malignancy

Pharmacological

Treatment Options

Localized prostate cancer

Low risk

• PSA <10, GS 6, cT1c, Life expectancy > 10y
• Active surveillance: 6 monthly PSA, DRE every 6 to12 months, Prostate biopsy every 1 to 3 years.
• Radical prostatectomy
• External beam radiation therapy (EBRT)
• Brachytherapy

Intermediate risk

• PSA 10 - 20, GS 7, cT2a/T2c, Life expectancy > 10yrs
• Active surveillance (low-tier IR GS 3+4)
• Radical prostatectomy
• External beam radiation therapy + Androgen deprivation therapy (ADT) 4-6 months
• Brachytherapy

High risk:

• PSA >20, GS 8-10, cT3/T4
• Neoadjuvant ADT + EBRT + Adjuvant ADT
• Radical prostatectomy + pelvic lymph nodes dissection

Metastatic Disease

• Castrate – naïve
• First treatment is castration:
• bilateral orchidectomy or Goserelin
• Docetaxel + Prednisolone +/- Abiraterone for high volume disease
• Abiraterone
• Enzalutamide
• Ketoconazole
• Bicalutamide
• Castrate Resistant
• Abiraterone
• Docetaxel
• Enzalutamide
• Cabazitaxel

Bone disease: Palliative radiotherapy, Zoledronic acid, Denosumab, Analgesia. Pathological fractures should be jointly assessed and managed with Orthopaedic team for possible stabilization.

HEAD AND NECK CANCER

Clinical Description

These involve the following malignancies:

• Oral cavity cancers: Buccal, gingival, retro-molar trigone, hard palate, oral tongue and floor of mouth
• Oropharynx: Tonsil, soft palate, Base of Tongue
• Nasopharynx
• Hypopharynx
• Larynx
• Salivary gland: Parotid, submandibular, submental

Signs and Symptoms

• Depends on specific location of the cancer.
• Non healing ulcers in the mouth, which easily bleed
• Associated difficulties in mastication and progressive dysphagia
• Neck mass/lymphadenopathy
• Otalgia
• Nasal blockage and bleeding
• Trismus
• Persistent cough
• Stridor
• Hoarseness of voice in advanced cases.

Investigations

• Done in conjunction with ENT surgeons and pathologists.
• Clinic: Complete upper airway assessment using Indirect Laryngoscopy +/- Flexible

Nasal Endoscopy

• Radiological imaging forms part of work up e.g. Panorex, CT Scan Base of skull to upper chest
• Biopsy: primary mass or suspicious lymph nodes

Non-pharmacological

• Depends on the extent of disease.
• Local therapies: Early-stage disease (T1/T2) can use single modality i.e. surgery or radiotherapy
• Advanced cases T3/T4: chemo- radiation is preferred to surgery for cosmesis and organ preservation. If recurrence, then surgery is treatment of choice.

Pharmacological

Drugs of choice: Cisplatin, Paclitaxel, Docetaxel, Gemcitabine, 5FU, Methotrexate, Cetuximab, Doxorubicin

• Follow up with routine clinical examinations and CT scans at scheduled visits.

HEMATOLOGICAL MALIGNANCIES

Clinical Description

• Currently lymphoma is the commonest hematological malignancy in Malawi.

Aggressive Non-Hodgkin’s Lymphomas such as HIV associated diffuse large cell lymphoma (DLCL) and Burkitt-like Leukemia/lymphoma (BL/L) and Hodgkin

Lymphoma. Other hematological malignancies include Leukemias and Multiple

Myeloma.

• Patients with hematological malignancies may present with cytopenias (reduced blood cell counts) or cytoses (increased blood cell counts), lymphadenopathy, splenomegaly and/or hepatomegaly. These may result in constitutional symptoms, infections, severe anemia and/or bleeding.
• Many other common conditions such as infections (e.g. TB) and solid malignancies will present with these features.
• Commonly patients with haematological malignancies are put on antibiotics for bacterial infections or on TB treatment which fail to resolve their clinical problems and, unless corrected in time, may delay appropriate treatment beyond "curative" stages.

All abnormal FBC results need peripheral blood film (PBF) examination

Bone Marrow Investigations

• Although we are only able to do morphological examination of bone marrow aspirates and biopsies in Malawi, bone marrow examination contributes significantly to the diagnosis of hematological conditions in our environment.
• Lymphoma, although not a primary problem of the bone marrow, may involve both the bone and marrow.
• Other malignancies may also spread to the bone marrow.

Histopathology

• The diagnosis of lymphomas also commonly requires biopsy of other tissues such as lymph nodes.

Flow cytometry

• Flow cytometers are used for CD4 and CD8 enumeration in the care of HIV infected patients in the country.
• Used to diagnose leukemia’s from peripheral blood or bone marrow aspirates.

Tumor Lysis Syndrome

Rapid cell turnover/breakdown occurring spontaneously or following treatment may result in this metabolic syndrome characterized by hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia +/-renal dysfunction.

• • Prophylaxis to include: Allopurinol 100 -300 mg o.d p.o., aggressive fluid resuscitation
• • Monitor the above biochemical parameters especially in patients with high grade and or bulky disease.