Telemedicine Nutritional Counseling for Cancer Cachexia in Pakistan

BACKGROUND AND RATIONALE Cancer cachexia is a metabolic syndrome characterized by progressive involuntary weight loss, skeletal muscle depletion, systemic inflammation, and anorexia, affecting 50-80% of cancer patients and contributing to 30% of cancer-related deaths. International guidelines from ESPEN and ASCO recommend nutritional counselling as a cornerstone of multimodal cachexia management; however, high-quality randomized evidence remains limited, particularly in low-and-middle-income countries.

In Pakistan, 31-97% of cancer patients experience malnutrition, compounded by geographic barriers, critical shortage of trained clinical nutritionists, and catastrophic out-of-pocket healthcare expenditure. No randomized controlled trial has evaluated telemedicine-delivered nutritional counselling for cancer cachexia anywhere in South Asia, representing a critical evidence gap.

STUDY DESIGN Single-centre, parallel-group, pilot randomized controlled trial with 1:1 allocation. Randomization is computer-generated with variable block sizes (4-6), stratified by cancer type (gastrointestinal vs. non-gastrointestinal) using sequentially numbered sealed opaque envelopes. The trial uses a single-blind design: outcomes assessors, laboratory staff, and the statistician are blinded to group allocation; participants and dietitians cannot be blinded due to the nature of the intervention.

INTERVENTION RATIONALE Both arms receive identical nutritional counselling content from the same registered dietitians following standardized ESPEN-based protocols (energy ≥25 kcal/kg/day; protein ≥1.0 g/kg/day), with culturally adapted Pakistani meal plans. Sessions are delivered bi-weekly at equal frequency (7 sessions over 12 weeks) so that delivery modality - not counselling dose - is the sole variable under study. The telemedicine arm uses WhatsApp Video Call as the primary platform (given its widespread use and low-bandwidth requirements in Pakistan), with Zoom or Microsoft Teams as alternatives. Patients participate from home; dietitians conduct sessions from a dedicated workspace at the Department of Medical Oncology, KEMU.

NON-INFERIORITY RATIONALE Given that both groups receive equivalent counselling frequency and content, a non-inferiority design is appropriate. The non-inferiority margin of -1.0 kg for body weight change at 12 weeks was selected based on clinical judgment and published cachexia literature, representing the maximum weight difference that would still be considered clinically acceptable for telemedicine to be adopted as a delivery alternative. Telemedicine will be declared non-inferior if the lower limit of the 95% confidence interval for mean weight difference (telemedicine minus standard care) exceeds -1.0 kg.

SAMPLE SIZE Using G*Power for an independent samples t-test: Cohen's d = 0.75, α = 0.05 (two-sided), power = 85%, yields 29 participants per group. Adjusted for 20% anticipated dropout in cancer cachexia trials, the final sample is 40 per group (80 total), with an expected evaluable sample of 64 participants.

STATISTICAL ANALYSIS Primary analysis is intention-to-treat. The primary outcome (body weight change, baseline to Week 12) will be analysed using an independent samples t-test or Mann-Whitney U test as appropriate, with ANCOVA adjusting for baseline weight, cancer type, ECOG performance status, and treatment changes during the study. Missing data will be handled by multiple imputation using chained equations (20 imputations) for <20% missingness, with complete case analysis as a sensitivity check. Per-protocol analysis (participants completing ≥75% of sessions) will be conducted as a secondary analysis. Exploratory subgroup analyses are planned by cancer type, baseline cachexia severity, sex, and urban versus rural residence.

SIGNIFICANCE This is the first RCT of telemedicine nutritional counselling for cancer cachexia in South Asia. The design isolates the effect of delivery modality by equalizing counselling frequency across arms. Results will provide effect size estimates to power a larger multi-centre trial, cost-effectiveness data for health policy decisions, and a scalable evidence-based model for nutritional care delivery in resource-constrained settings.

Inclusion criteria

• 1. Age and Consent Capacity

• Age ≥18 years (adults of either biological sex or gender identity)
• Able to understand study procedures and provide written informed consent independently or with assistance from legally authorized representative 2. Cancer Diagnosis
• Histologically or cytologically confirmed solid tumor malignancy of any type, including but not limited to:

• Lung cancer (non-small cell or small cell)
• Breast cancer
• Gastrointestinal cancers: gastric (stomach), colorectal, pancreatic, esophageal, hepatobiliary (liver, gallbladder, bile duct)
• Head and neck cancers (oral cavity, pharynx, larynx, nasal cavity, salivary glands)
• Gynecological cancers: cervical, ovarian, endometrial, vulvar, vaginal
• Genitourinary cancers: prostate, bladder, renal (kidney), testicular
• Other solid tumors: sarcomas, melanoma, thyroid, brain tumors
• Any cancer stage eligible (Stage I, II, III, or IV) 3. Cancer Cachexia
• Documented unintentional weight loss meeting at least one of the following criteria:

• Weight loss ≥3% of body weight within the past 3 months, OR
• Weight loss ≥5% of body weight within the past 6 months
• Weight loss must be documented by medical records, patient self-report, or measurement at screening visit compared to documented previous weight 4. Active Cancer Treatment
• Currently receiving active anti-cancer treatment, OR
• Scheduled to begin active anti-cancer treatment within 2 weeks of enrollment
• Eligible anti-cancer treatments include:

• Chemotherapy (cytotoxic agents, any regimen)
• Radiation therapy (external beam or brachytherapy)
• Targeted molecular therapy (tyrosine kinase inhibitors, monoclonal antibodies)
• Immunotherapy (checkpoint inhibitors, CAR-T cell therapy)
• Hormonal therapy for hormone-sensitive cancers
• Combination therapies
• Patients receiving palliative/supportive care only (without active anti-cancer treatment) are excluded 5. Performance Status
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2:

• Grade 0: Fully active; able to carry on all pre-disease activities without restriction
• Grade 1: Restricted in physically strenuous activity but ambulatory; able to carry out light or sedentary work (e.g., light housework, office work)
• Grade 2: Ambulatory and capable of all self-care activities but unable to carry out any work activities; up and about >50% of waking hours 6. Technology Access and Literacy
• Access to a smartphone or tablet device with video calling capability (personal device or family member's device that participant can use)
• Reliable internet connectivity available via at least one of:

• Home Wi-Fi network
• Mobile cellular data plan (3G, 4G, or 5G)
• Access to public/community Wi-Fi
• For telemedicine group: willingness and ability to participate in video consultations 7. Language
• Able to communicate verbally in Urdu (national language of Pakistan) or English
• Able to understand spoken instructions and questions
• Literacy not required; illiterate participants eligible with assistance from family/witness for consent and questionnaires 8. Geography
• Able to attend in-person assessments at King Edward Medical University/Mayo Hospital, Lahore, Pakistan at baseline (Week 0) and Week 12
• For telemedicine group: only 2 hospital visits required (Weeks 0 and 12)
• For standard care group: able to attend 7 hospital visits (Weeks 0, 2, 4, 6, 8, 10, 12) 9. Commitment
• Willing to participate in the study for the full 12-week duration
• Willing to comply with study procedures including dietary assessments, questionnaires, blood tests, and nutritional counseling sessions

Exclusion criteria

• Inability to Eat Orally

• Severe dysphagia (difficulty swallowing) requiring enteral nutrition support via:

• Nasogastric tube feeding
• Percutaneous endoscopic gastrostomy (PEG) tube
• Jejunostomy tube
• Complete bowel obstruction preventing oral intake
• Total parenteral nutrition (TPN) as sole nutritional support
• Note: Partial oral intake supplemented with enteral nutrition is eligible if patient can consume at least some food by mouth 2. Refractory Cachexia
• ECOG Performance Status 3 or 4:

• Grade 3: Capable of only limited self-care; confined to bed or chair >50% of waking hours
• Grade 4: Completely disabled; cannot carry out any self-care; totally confined to bed or chair
• Active cachexia management deemed not clinically appropriate or futile by treating oncologist
• Estimated life expectancy <3 months per treating oncologist's assessment
• Imminent end-of-life care or transition to hospice care 3. Uncontrolled Comorbid Conditions
• Uncontrolled diabetes mellitus defined as:

• Glycated hemoglobin (HbA1c) >9% within past 3 months, OR
• Frequent hypoglycemic or hyperglycemic episodes requiring emergency care
• Rationale: Uncontrolled diabetes affects nutritional metabolism and requires specialized dietary management beyond scope of this intervention
• End-stage renal disease requiring dialysis (hemodialysis or peritoneal dialysis)

o Rationale: Dialysis patients require specialized renal diet with protein, fluid, potassium, and phosphorus restrictions that differ substantially from cancer cachexia nutritional recommendations

• Severe heart failure, New York Heart Association (NYHA) Functional Class IV:

• Symptoms at rest; any physical activity causes discomfort
• Rationale: Severe cardiac cachexia has different pathophysiology and requires cardiology-directed nutritional management 4. Psychiatric or Cognitive Impairment
• Active psychiatric illness that would preclude meaningful participation or informed consent, including:

• Severe major depressive disorder with active suicidal ideation
• Acute psychotic episode (schizophrenia, bipolar disorder with psychosis)
• Severe anxiety disorder preventing participation in counseling sessions
• Cognitive impairment preventing informed consent or ability to participate, including:

• Advanced dementia (moderate to severe; unable to follow simple instructions)
• Severe delirium (acute confusional state)
• Significant brain metastases causing cognitive dysfunction
• Note: Mild cognitive impairment or controlled psychiatric conditions with stable treatment are not exclusionary 5. Concurrent Study Participation
• Currently enrolled in another interventional clinical trial testing nutritional interventions, dietary supplements, or appetite stimulants
• Rationale: Concurrent nutritional interventions would confound outcome assessment
• Note: Participation in observational studies, cancer treatment trials (chemotherapy, radiation), or non-nutritional supportive care trials is permitted 6. Pregnancy or Lactation
• Pregnant women (confirmed by urine or serum pregnancy test if reproductive potential)
• Breastfeeding/lactating women
• Rationale: Pregnancy and lactation have substantially different and increased nutritional requirements that require specialized prenatal/postnatal nutritional counseling beyond the scope of cancer cachexia management in this protocol 7. Severe Food Allergies or Intolerances
• Known severe allergy or intolerance to recommended nutritional supplements (oral nutrition supplements, protein powders, vitamins/minerals) for which no suitable alternatives are available in Pakistan
• Note: Common food allergies (dairy, eggs, nuts) are not exclusionary as alternative food sources can be recommended 8. Logistical Barriers
• Unable to attend baseline assessment visit (Week 0) at King Edward Medical University/Mayo Hospital, Lahore
• Unable to attend final assessment visit (Week 12) at the hospital
• For telemedicine group: Complete inability to access internet or use smartphone/tablet even with family assistance
• No reliable means of contact (no phone number, no address) 9. Other
• Enrolled in this study previously (re-enrollment not permitted)
• Non-cancer-related causes of weight loss that would confound cachexia assessment:

• Active eating disorder (anorexia nervosa, bulimia nervosa) requiring psychiatric treatment
• Intentional weight loss through dieting for weight management
• Hyperthyroidism causing unintentional weight loss (must be controlled before enrollment)
• Active gastrointestinal infection (parasites, chronic diarrhea from infectious cause)
• Any condition that, in the opinion of the principal investigator, would compromise patient safety, study integrity, or ability to complete study procedures