Introduction
Esophageal cancer stands as a formidable challenge in the global oncological landscape, representing the fourth leading cause of cancer-related mortality in India. While its incidence is shaped by complex regional dynamics, the disease is characterized by a high degree of virulence and a clinical presentation that is often dangerously delayed. In the Indian context, Squamous Cell Carcinoma (SCC) remains the dominant histological subtype, accounting for approximately 80% of cases. However, shifting lifestyle patterns and an increase in the prevalence of obesity and gastroesophageal reflux disease (GERD) have contributed to a rising incidence of adenocarcinoma, mirroring trends observed in high Human Development Index (HDI) nations [1,2].
The epidemiological profile of esophageal cancer in India is heavily influenced by socio-cultural and regional risk factors. Tobacco use in various forms-including cigarette smoking, hookah, and smokeless tobacco-remains a primary driver. In specific regions like Kashmir, unique dietary habits such as the consumption of hot salted tea with baking soda and sun-dried spices have been identified as significant contributors. Conversely, in regions like Punjab, studies have highlighted that even in populations where tobacco and alcohol use are less prevalent, such as among women, poor nutritional status and the consumption of scalding hot beverages serve as critical etiological factors [3].
The clinical hallmark of esophageal malignancy is progressive dysphagia, an obstructive symptom that begins with solids and inevitably advances to liquids. By the time patients seek medical intervention, they often present in a state of advanced cachexia. This profound weight loss is not merely a consequence of mechanical obstruction but is driven by a complex interplay of reduced oral intake, systemic inflammation, and the heightened metabolic demands of the tumor itself. Recent data from 2020 underscores the severity of this burden, with over 52,000 incident cases and a staggering mortality rate of approximately 46,000 fatalities annually in India [4].
Malnutrition in these patients is multifaceted, arising from both the direct effects of the tumor and the secondary toxicities of multimodal therapy. The standard of care, often involving concurrent chemoradiotherapy, can exacerbate nutritional decline through radiation-induced esophagitis, nausea, and vomiting [5]. This leads to a vicious cycle: malnutrition reduces the patient's tolerance for oncological treatment, resulting in dose reductions or treatment interruptions, which in turn compromises survival outcomes and increases postoperative morbidity. Studies have shown that skeletal muscle wasting during neoadjuvant therapy is an independent predictor of cancer recurrence and postoperative mortality [1] [2].
Given these challenges, the implementation of robust nutritional screening and intervention is paramount. The Patient-Generated Subjective Global Assessment (PG-SGA) has emerged as a gold-standard tool in this setting. Unlike generic screening methods, the PG-SGA combines patient-reported symptoms-such as nausea and dysphagia-with clinical assessments of muscle wasting and fat loss. This allows for a nuanced stratification of patients into categories ranging from well-nourished (Grade A) to severely malnourished (Grade C), necessitating aggressive nutritional support [7].
Current clinical guidelines, including those from the European Society for Clinical Nutrition and Metabolism (ESPEN), emphasize the superiority of enteral nutrition (EN) over parenteral nutrition (PN). EN maintains the integrity of the gastrointestinal barrier, reduces the risk of systemic infections, and is more physiologically appropriate for patients undergoing intensive therapy. Whether delivered via nasogastric tubes, surgical jejunostomy, or self-expandable metal stents, enteral access provides the essential conduit for metabolic support when the oral route is no longer viable [8].
Despite the clear association between nutritional status and clinical outcomes, there remains a need for more granular data regarding the optimal timing and route of enteral intervention in the Indian patient population. This study investigates the prevalence of moderate to severe malnutrition using the PG-SGA tool and evaluates the impact of intensely guided enteral nutrition on improving chemotherapy and radiotherapy tolerance among esophageal carcinoma patients at a tertiary care facility.
Materials and Methods
Study Design: This randomized, interventional, prospective study was conducted between July 2024 and December 2025 at the Sri Guru Ram Das Institute of Medical Sciences and Research.
Ethical Approval: The present research study received approval from the Institutional Ethics Committee (SGRD/IEC/2024-299) and the Institutional Research Committee of SGRDIMSR, Sri Amritsar.
Participant Selection: Histopathologically confirmed cases of esophageal carcinoma were recruited after obtaining informed written consent. Patients aged 18 years with histologically proven esophageal malignancy were inclusion, whereas patients who had undergone prior esophagectomy, those requiring total parenteral nutrition were excluded from the study.
Randomization and Grouping
A total of 60 participants (30 per group) were allocated into two cohorts using block randomization to ensure equal distribution:
Group A (Intervention): Moderate to severely malnourished patients receiving intensely guided enteral nutrition. Support involved personalized counseling by a dietitian, targeting a caloric intake of 25-35 kcal/kg/day and protein intake of 1.0-1.5 g/kg/day. Adherence was monitored through weekly in-person or telephonic consultations.
Group B (Control): Patients receiving standard nutritional advice at the time of initial presentation without intensive follow-up.
Nutritional and Clinical Assessment
Malnutrition was staged using the Patient-Generated Subjective Global Assessment (PG-SGA) [9]. This tool evaluated four key domains:
Weight History: Magnitude and rate of weight loss.
Food Intake: Changes in dietary patterns and consistency.
Nutrition Impact Symptoms: Cumulative burden of symptoms like dysphagia, nausea, and pain (scored up to 24 points).
Functional Capacity: Physical activity levels based on ECOG performance status. Objective biochemical surveillance included Hemoglobin, TLC, renal function tests, liver function tests, serum proteins (albumin/globulin), and electrolytes.
Treatment Protocol and Enteral Access
All patients with locally advanced disease received neoadjuvant chemoradiotherapy according to the CROSS protocol. Enteral access was established based on the severity of dysphagia: Oral: For patients capable of maintaining intake. Enteral: Endoscopically guided Ryle’s tube or surgical feeding jejunostomy for those with severe luminal obstruction.
Outcome Measures and Toxicity Grading
Patients were reassessed at 4 and 8 weeks using PG-SGA scores and biochemical parameters. Treatment tolerance was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, which grades toxicities from Grade 1 (mild) to Grade 5 (death) [10].
Statistical Analysis
Data were analyzed using appropriate statistical software. Continuous variables were expressed as mean ± SD and compared using independent t-tests. Categorical variables were expressed as frequencies and percentages, analyzed with Pearson’s Chi-square. A p-value <0.05 was considered statistically significant.
Results
A total of 60 patients with histopathologically proven esophageal carcinoma were analyzed and equally randomized into Group A (Intensely Guided Enteral Nutrition, n=30) and Group B (Standard Nutritional Counseling, n=30).
1. Baseline Clinicopathological Characteristics
The cohort exhibited a slight female predominance (51.7%). The majority of patients were aged 61 years or older (55%). Squamous cell carcinoma was the primary histological subtype (85%), and the lower thoracic esophagus was the most frequent tumor site (78.3%). At presentation, 50% of patients reported dysphagia to liquids, and the mean PG-SGA score (12.80±3.22) indicated a high baseline risk of severe malnutrition across both groups. Statistical analysis confirmed that both groups were comparable at baseline regarding age (p=0.249), gender (p=0.606), and BMI (p=0.258).
Table 1: Demographic and Clinical Profile of the Study Population (n=60)
| Characteristic | Category | Frequency (n) | Percentage (%) |
| Gender | Female | 31 | 51.7% |
| Male | 29 | 48.3% | |
| Histology | Squamous Cell Carcinoma | 51 | 85.0% |
| Adenocarcinoma | 9 | 15.0% | |
| Tumor Location | Lower Thoracic | 47 | 78.3% |
| Middle Thoracic | 10 | 16.7% | |
| Mid/Lower Thoracic | 3 | 5.0% | |
| Dysphagia | Solids | 23 | 38.3% |
| Semi-solids | 7 | 11.7% |
2. Longitudinal Nutritional and Hematological Outcomes
Intensely guided nutrition in Group A led to superior recovery of anthropometric and biochemical markers compared to standard care. Group A demonstrated a significant progressive weight gain of +3.73 kg by week 8 (p=0.008), whereas Group B experienced significant early weight loss by week 4 (-1.67 kg, p=0.002) with no significant recovery.
Table 2: Comparison of Nutritional and Hematological Trends Over 8 Weeks
| Parameter | Group | Baseline (Mean±SD) | 8 Weeks (Mean±SD) | Change | p-value* |
| Weight (kg) | Group A | 56.17±6.53 | 59.90±3.20 | +3.73 | 0.008 |
| Group B | 57.23±7.65 | 57.27±5.05 | -0.03 | 0.985 | |
| BMI (kg/m2) | Group A | 20.10±3.16 | 21.45±2.52 | +1.35 | 0.008 |
| Group B | 19.26±2.53 | 19.44±3.23 | +0.18 | 0.760 | |
| PG-SGA Score | Group A | 12.40±3.22 | 9.47±1.94 | -2.93 | <0.001 |
| Group B | 13.20±3.22 | 10.53±2.16 | -2.67 | <0.001 | |
| Hemoglobin (g/dL) | Group A | 9.23±1.29 | 10.44±1.17 | +1.21 | 0.002 |
| Group B | 9.92±1.36 | 7.13±0.92 | -2.79 | <0.001 | |
| Albumin (g/dL) | Group A | 3.20±0.25 | 3.7±0.43 | +0.53 | <0.001 |
| Group B | 3.52±0.20 | 3.26±3.74 | -0.26 | 0.709 | |
| *p-value represents significance of change from baseline to 8 weeks within each group. |
3. Treatment Tolerance and Adverse Events
Treatment-related toxicities were graded using CTCAE v5.0. While both groups encountered adverse events, Group A showed a significantly lower incidence of Grade 3 (severe) toxicities compared to Group B (40.0% vs. 80.0%). Interestingly, Group A had more documented Grade 4 events, likely reflecting the ability of these nutritionally supported patients to persist with intensive therapy cycles that might otherwise have been discontinued in malnourished counterparts.
Table 3: CTCAE Adverse Event Distribution Between Groups
| Toxicity Grade | Group A (%) | Group B (%) | Total |
| Grade 1 (Mild) | 2 (6.7%) | 1 (3.3%) | 3 |
| Grade 2 (Moderate) | 6 (20.0%) | 4 (13.3%) | 10 |
| Grade 3 (Severe) | 12 (40.0%) | 24 (80.0%) | 36 |
| Grade 4 (Life-threatening) | 10 (33.3%) | 1 (3.3%) | 11 |
| Total | 30 (100%) | 30 (100%) | 60 |
| Statistical Analysis: chi2 = 12.097; df=3; p=0.007 |
The results indicate that intensely guided enteral nutrition effectively reverses the catabolic state, improves hematological parameters, and significantly alters the profile of treatment-related toxicities in esophageal cancer patients undergoing therapy.
Discussion
The demographic and clinical characteristics of the study population (N=60) demonstrate a slight female predominance (51.7%) and a significant prevalence of Squamous Cell Carcinoma (SCC) (85.0%), primarily localized in the lower thoracic esophagus (78.3%).
The study shows a near-equal gender distribution with a slight female lead (51.7%). This is a notable different from global data where esophageal cancer typically shows a strong male predilection, often cited at a 3:1 or 4:1 ratio. Recent epidemiological shifts in Southeast Asia and parts of Africa have noted an increasing incidence in women, often linked to environmental exposures and nutritional deficiencies as reported by Morgan et al.,[11].
The majority of cases are Squamous Cell Carcinoma (85%), with Adenocarcinoma (AC) accounting for only 15% (Table 1)). This aligns perfectly with the "Esophageal Cancer Belt" (spanning from Central and South Asia to Northern China), where SCC remains the dominant histological subtype. In contrast, Western populations (USA, UK) have seen a dramatic shift where Adenocarcinoma now accounts for over 60-70% of cases due to rising rates of obesity and GERD as reported by Bray et al.,[12].
In the current study the Lower Thoracic region was the most common site (78.3%) (Table 1)). This finding is interesting because SCC is historically distributed more evenly across the middle and upper thirds of the esophagus. However, recent surgical series have reported an uptick in lower-third SCC, which can sometimes pose a diagnostic challenge in differentiating it from Siewert type I gastroesophageal junction tumors Ajani et al.,[13].
Smyth et al.,[14] reported progressive dysphagia is the hallmark of esophageal malignancy, usually indicating that at least two-thirds of the esophageal circumference is involved. The data suggests a population presenting at a stage where mechanical obstruction is significant but not yet absolute (as semi-solid dysphagia was lower at 11.7%), in the present study solids dysphagia was the primary presenting symptom (38.3%).
In the present study Group A showed a significant weight gain (+3.73 kg; p=0.008) and BMI increase (+1.35kg/m²; p=0.008), whereas Group B remained static (Table 2). Weight maintenance or gain is a critical prognostic factor in oncology. Significant increases in BMI often correlate with improved tolerance to chemotherapy and reduced surgical complications as reported Muscaritoli et al.,[15].
Both groups showed a significant reduction in PG-SGA scores (p < 0.001), indicating an improvement in perceived nutritional symptoms and functional status (Table 2). Isenring et al.,[7] reported PG-SGA score is the gold standard for oncology nutrition. A decrease in score signifies a reduction in nutrition-impact symptoms (like nausea or loss of appetite).
In the present study Group A showed significant rise in Hemoglobin (+1.21 g/dL, p=0.002) and Albumin (+0.53 g/dL, p<0.001) similar findings by Zhang et al.,[16], who demonstrated that enteral supplementation effectively stabilizes the HALP (Hemoglobin, Albumin, Lymphocyte, Platelet) score, a known independent predictor of overall survival in esophageal cancer.
The distribution of adverse events according to CTCAE reveals a statistically significant difference in toxicity profiles between the two cohorts. While Group B showed a disproportionately high incidence of Grade 3 (Severe) toxicities (80.0%), Group A demonstrated a shift toward Grade 4 (Life-threatening) events (33.3%) despite having fewer Grade 3 complications. This pattern suggests that while the intervention in Group A may mitigate the high volume of severe (Grade 3) side effects often seen in standard oncological care, it may also be associated with a subset of more intensive clinical challenges.
Li et al.,[17] reported that esophageal cancer patients undergoing standard chemoradiotherapy without aggressive nutritional or supportive intervention frequently experience severe dysphagia and hematological toxicity.
Conclusion
In the present study, the findings demonstrate that intensely guided enteral nutrition plays a crucial role in mitigating nutritional decline by stabilizing body weight, improving PG-SGA scores, and maintaining biochemical parameters. Furthermore, intensely guides nutritional support enhances tolerance to chemoradiotherapy and contribute to improved overall outcomes. These results underscore the importance of intensely guided nutrition ultimately improving quality of life and potentially survival.
Declarations
Ethical Approval and Consent to Participate
All procedures performed in this case series were conducted in accordance with institutional ethical standards and the principles of the Declaration of Helsinki. Ethical approval was obtained from the appropriate institutional review board where required. Written informed consent was obtained from all patients or their legal guardians prior to the procedures.
Consent for Publication
Written informed consent for publication of clinical details and images was obtained from the patients or their legal guardians. All identifying information has been anonymized to protect patient confidentiality.
Availability of Supporting Data
The data supporting the findings of this study are available from the corresponding author upon reasonable request, subject to institutional and ethical regulations.
Competing Interests
The authors declare that they have no competing interests related to this work.
Funding
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Authors’ Contributions
All authors contributed substantially to the conception, data acquisition, analysis, drafting, and critical revision of the manuscript. All authors have read and approved the final version of the manuscript.