Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand

Narisara Phansila; Chaiyasit Sittiwet; Ranee Wongkongdech

doi:10.12688/f1000research.75060.2

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Research Article

Revised

Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand

[version 2; peer review: 1 approved, 1 approved with reservations]

Narisara Phansila¹, Chaiyasit Sittiwet¹, Ranee Wongkongdech¹

PUBLISHED 09 Apr 2025

Author details Author details

¹ Faculty of Medicine, Mahasarakham University, Mahasarakham, 44000, Thailand

Narisara Phansila
Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation

Chaiyasit Sittiwet
Roles: Conceptualization, Supervision

Ranee Wongkongdech
Roles: Conceptualization, Project Administration, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Oncology gateway.

Abstract

Background

Cholangiocarcinoma (CCA) has a poor prognosis and is a major cause of mortality and suffering in Thailand’s Northeastern (Isaan) Region.

Methods

This prospective cohort study aimed to compare the health-related quality of life (HRQoL) among 72 newly diagnosed CCA patients; 42 patients who received cannabis treatment (CT) and 30 patients who received a standard palliative care treatment (ST). The study was carried out between 1^st September 2019 to 31^st October 2020. Data were collected from patients from oncology clinics of six hospitals in five provinces of northeast Thailand. The HRQoL was measured at baseline, and at 2 and 4 months after diagnosis by the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaires QLQ-C30, and QLQ-BIL21. The Mann-Whitney U-test was performed to compare quality of life scores between the two patient groups and Wilcoxon signed rank test was performed to compare within groups QoL scores at pre-treatment, and 2 and 4 month follow-ups.

Results

Global health status and functional scales, for both groups were high at pre-treatment. At 2 and 4 month follow-up, CT group patients had consistent statistically significantly better Palliative Performance Scale (PPS), and QoL scores, and many symptom scores than the ST group.

Conclusions

Medicinal cannabis may increase QoL for advanced CCA patients. Our findings support the importance of early access to palliative cannabis care clinic before the terminal and acceleration phase close to death.

Keywords

Quality of life, Cholangiocarcinoma, medicinal cannabis, Northeastern Thailand

Corresponding author: Ranee Wongkongdech

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2025 Phansila N et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Phansila N, Sittiwet C and Wongkongdech R. Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2025, 11:20 (https://doi.org/10.12688/f1000research.75060.2) First published: 10 Jan 2022, 11:20 (https://doi.org/10.12688/f1000research.75060.1) Latest published: 09 Apr 2025, 11:20 (https://doi.org/10.12688/f1000research.75060.2)

Revised Amendments from Version 1

This revised version incorporates substantial changes in response to peer reviewer feedback. The Methods section was expanded to include detailed information on sample size calculation, participant enrolment procedures, treatment protocols for both the standard and cannabis-based care groups, and the rationale for instrument selection. Specifically, the EORTC QLQ-C30 and QLQ-BIL21 were justified as appropriate HRQoL tools, with the Palliative Performance Scale (PPS) added to assess functional status. The statistical analysis section was revised to explain the use of non-parametric methods and discuss alternatives such as generalized estimating equations (GEE) for future research. Additionally, clarifications were made regarding the imbalanced baseline characteristics and their implications. The Discussion section was restructured to emphasize HRQoL as the primary outcome, address key findings more concisely, and align with the study objectives. References were updated, inconsistencies were corrected, and minor revisions were made to improve clarity, coherence, and readability throughout the manuscript.

See the authors' detailed response to the review by Ueamporn Summart

Introduction

Cholangiocarcinoma (CCA) is a rare liver tumor worldwide (incidence <6 cases per 100,000), but, is highly prevalent in parts of Thailand.¹ The Northeastern (Isaan) region of Thailand has > 85 cases per 100,000, especially in Khon Kaen Province with 118.5 cases per 100,000 populations. Which is 100 times higher than the global rate.² Typically, CCAs are asymptomatic in the early stages, and are consequently not diagnosed until late stage when the cancer has already metastasized, severely limiting effective therapeutic options and becoming a major cause of mortality.³ For these patients, palliative treatments such as chemotherapy or supportive care are standard, and median survival ranges from 4 to 6 months⁴^,⁵; 5 and the 6-month survival is only 35%.⁵ The major surgical treatments are surgical resection and/or liver transplantation, whereas chemotherapies are virtually palliative given the typical late-stage diagnosis and marked chemo-resistance of this cancer.⁶

Health-related quality of life (HRQoL) is a multidimensional concept encompassing physical, emotional, and social well-being, and is a key outcome in cancer care.⁷ Among advanced cholangiocarcinoma (CCA) patients, pain and sleep disturbances are particularly common and have been strongly associated with impaired HRQoL.⁸^–¹⁰ Persistent pain not only limits physical functioning but also disrupts sleep, contributing to fatigue, anxiety, and emotional distress.¹¹^,¹² This symptom burden creates a cycle that further reduces overall quality of life, especially in palliative care settings. Effective management of pain and sleep-related symptoms is therefore critical in improving HRQoL for these patients.

Medical cannabis has been used in palliative care to alleviate pain, relieve nausea and stimulate appetite,¹³ and has been shown to attain good symptom control and reduce the number of palliative care drugs used.¹⁴ A recent oncology study on the short-term outcomes of medical cannabis showed significant improvement in multiple symptoms between baseline and one-month follow-up, including reductions in pain intensity, affective and sensory pain, improved sleep quality and duration and reduced cancer distress, and both physical and psychological symptom burden.¹⁵ However, no studies have yet compared the quality of life of patients with advanced CCA treated with, either, a standard palliative-care treatment protocol, or, with medical cannabis.

Thailand was the first country in Southeast Asia to approve cannabis for medical treatment.¹⁶ Currently, in Thailand, there are two palliative care treatment protocols allowed for cancer patients; standard treatment regime, and medical cannabis treatment. As there is no comparative Thai research yet on HRQoL from the perspective of patients, this study was designed to compare the perceived quality of life outcomes between the two treatment protocol options.

Study design and participants

Sample size calculation

The primary outcome of this study was the difference in health-related quality of life (HRQoL) scores between the cannabis treatment (CT) group and the standard treatment (ST) group over time. HRQoL was measured using the EORTC QLQ-C30 and QLQ-BIL21 at three time points: baseline, 2 months, and 4 months post-treatment.

To determine an adequate sample size for detecting significant differences between the groups, we used a two-sample t-test formula. As the comparisons were planned at three time points, we applied Bonferroni correction to adjust for multiple testing, setting the alpha level at 0.017 (0.05/3). Parameters were drawn from a pilot study involving 15 patients per group with similar characteristics. The estimated standard deviation (σ) was 13.55 and the minimal clinically important difference (Δ) in QoL scores was assumed to be 10 points. The sample size calculation with 80% power (β = 0.20) and α = 0.017 yielded a minimum of 30 participants per group.

To account for potential loss to follow-up, especially given the advanced disease stage, we initially recruited 45 patients per group. This allowed for an estimated 50% attrition rate while ensuring that at least 30 participants remained in each group at the 4-month endpoint ( Figure 1).

Figure 1. Flow diagram of participants throughout the course of the study.

CCA = Cholangiocarcinoma; PPS = Palliative performance scale; ST = Standard treatment; CT= Cannabis treatment.

Participant enrollment and treatment procedures

Cholangiocarcinoma (CCA) out-patients were enrolled in this prospective cohort study from September 2019 to October 31, 2020, from six hospitals across five provinces in Northeastern Thailand (Roi-Et Regional Hospital, Burirum Regional Hospital, Surin Provincial Hospital, Sawang Dandin Crown Prince Hospital, Panna Nikhom Hospital, and Pana Hospital). Participants were recruited by clinicians upon diagnosis of advanced-stage CCA, confirmed by at least one of the following diagnostic procedures: ultrasonography (U/S), computerized tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP),¹⁷ or histology. Eligibility criteria included a Palliative Performance Scale (PPS) score of >50, corresponding to an estimated life expectancy of more than 60 days.

After diagnosis, treatment options such as chemotherapy, surgery, radiotherapy, standard palliative care, and medical cannabis were explained to patients. Based on informed choice, patients were assigned to either the hospital’s palliative care clinic or medical cannabis clinic. Exclusion criteria included PPS <30,¹⁸ cognitive impairment, hospitalization during follow-up, refusal to continue, or loss to follow-up.

Standard palliative care treatment

Patients in the standard treatment (ST) group received care according to national palliative care guidelines. This included symptom-directed management such as opioid and non-opioid analgesics for pain, antiemetics for nausea, laxatives, nutritional support, psychological counseling, and optional palliative chemotherapy or radiotherapy where appropriate. Multidisciplinary palliative care teams delivered services.

Medical cannabis treatment

These cannabis regimens were administered under the Thai Ministry of Public Health’s clinical cannabis protocol, which includes dosing guidelines, adverse effect monitoring, and follow-up as outlined in official regulatory documents.¹⁹^,²⁰ Patients were monitored using the Edmonton Symptom Assessment System (ESAS) at each visit, and dose titration was adjusted based on symptom response and tolerability.

The medical cannabis treatment (CT) group received care under Thailand’s Ministry of Public Health regulations. Three cannabis extract regimens were used: 1) THC (12.5 mg/ml), 2) THC: CBD 1:1 (THC 27 mg/ml: CBD 25 mg/ml), and 3) DTAM Ganja Oil (THC 2 mg/ml ± CBD 0.5 mg/ml). Patients were cannabis-naive and followed a titration approach based on the “start low, go slow, stay low” principle.²¹ Dosing began with the lowest effective amount, adjusted every 1–2 days until symptom relief was achieved. Adverse effects triggered dose reduction or discontinuation. The protocol included drug holidays and ESAS (Edmonton Symptom Assessment System) monitoring.

Eligibility for cannabis included terminal cancer, COPD, or AIDS diagnoses without contraindications. Prescriptions were authorized by trained medical or Thai traditional medicine practitioners.

Instrument and QoL assessment

HRQoL and functional status were assessed using the EORTC QLQ-C30 (version 3.0), the disease-specific QLQ-BIL21 module, and the Palliative Performance Scale (PPS) at baseline, 2 months, and 4 months. These instruments were selected based on their strong validation in oncology populations, availability in Thai translations validated for clinical use, and their specific applicability to cholangiocarcinoma-related symptoms.²²^,²³ While the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) is also a disease-specific tool,²⁴ the EORTC QLQ-C30 and QLQ-BIL21 were preferred in this study because they are widely used in international and Thai clinical studies, and the QLQ-BIL21 specifically captures biliary-related symptom burden such as jaundice, weight loss, eating difficulties, and anxiety.²⁵ Scoring followed EORTC guidelines, with higher scores indicating better function or higher symptom burden depending on the scale. Patients were categorized into QoL groups: <33 = low QoL, >66 = high QoL for functional scales; the reverse applied for symptom scales.²⁶^,²⁷ Additionally, the Palliative Performance Scale (PPS) was used to evaluate patients’ functional status and eligibility. PPS has demonstrated prognostic utility in palliative care settings and complemented HRQoL measures in understanding patient condition across time.²³

Data collection and quality control

The QOL data was collected by specially trained research assistants in each hospital at the time of enrollment into the study, and by the researcher in hospital, or, in the community among survivors at 2- and 4-months’ post-treatment. Research monitoring and quality control procedures included the researcher observing research assistants’ first interview before treatment and researcher carrying out follow-up interviews at 2- and 4-months post-treatment commencement.

Data analysis

Descriptive statistics were used to summarize demographic and clinical characteristics. Due to data characteristics, the primary outcome, HRQoL score differences between groups and over time, was analyzed using non-parametric methods. The Mann-Whitney U test was used for between-group comparisons, and the Wilcoxon signed-rank test was applied for within-group comparisons across time points.

These non-parametric tests were selected based on assumption testing, which revealed non-normal distributions of HRQoL scores (as confirmed by Shapiro-Wilk tests and Q-Q plots), particularly at follow-up time points. Because several questionnaire items were ordinal, non-parametric methods were considered more appropriate than parametric tests.

While non-parametric methods were used due to distributional concerns, we acknowledge the potential for within-subject correlation over time. Future studies with larger samples may consider using generalized estimating equations (GEE) to model repeated measures and account for time-dependent covariates more robustly. All analyses were conducted using SPSS version 24.

Ethical review

This research was approved by the Maha-Sarakham University Human Research Ethics Committee (Reference NO.204/2563), Roi-Et Regional Hospital, and Burirum Regional Hospital (Reference RE064/2563). Ethics Committees for Human Research, based on the Declaration of Helsinki and the ICH GCP guidelines Written informed consent was obtained from all patients.

Results

Initially, 52 patients chose a standard treatment (ST), and 63 patients chose medical cannabis treatment (CT), all with Palliative Performance Scores (PPS) > 50. However, by the four-month follow-up point, there were only 72 patients remaining (21 dropped out at the 2 ^nd month, and a further 12 at 4 months), leaving 30 patients in the ST group and 42 in the CT group, respectively. In total, 30 patients were in the ST group (15 males and 15 females) and 42 patients in the CT group (27 males and 15 females). Their mean ages were 66.03 (S.D. = 11.46) and 65.80 years (S. D. = 10.55), respectively. Most patients were single/widowed (66.64%/59.52%) and worked in agriculture (50.0%/52.38%). Mean PPS scores were 79.33 (S.D. = 5.83) and 80.23 (S.D. = 12.78), respectively. Table 1 displays fuller demographic characteristics of the 72 CCA patients.

Table 1. Participant characteristics (n = 72).

Variable	Number of ST (%)	Number of CT (%)
Variable	[n = 30]	[n = 42 (%)]
Sex
Male	15 (50.00	27 (64.30)
Female	15 (50.00)	15 (35.70)
Age (year) mean (S.D.)	66.03 (11.46)	65.80 (10.55)
<60	7 (23.33)	13 (31.00)
60-69	13 (43.34)	13 (31.00)
>70	10 (33.33)	16 (38.00)
Min, max	38, 89	35, 89
Status
Single/widowed	20 (66.64)	25 (59.52)
Married	10 (33.33)	17 (40.48)
Occupation
Agriculture	15 (50.00)	22 (52.38)
Government	10 (33.33)	12 (28.57)
Other	5 (16.64)	8 (19.05)
PPS [mean (S.D.)]	79.33 (5.83)	80.23 (12.78)
50-70	6 (20.00)	15 (35.70)
80-100	24 (80.00)	27 (64.30)
Min, max	70, 90	60, 100

Comparison of variables in EORTC QLQ-C30, QLQ-QLQ-BIL21 at the pre-treatment, 2^nd and 4^th month treatment ( Table 2).

Table 2. Comparison of variables in European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30, QLQ- QLQ- BIL 21 (Pre-treatment, 2^nd and 4^th month treatment).

variables	Pre-treatment			2^nd month treatment			4^th month treatment
variables	Standard	Cannabis	P value	Standard	Cannabis	P value	Standard	Cannabis	P value
PPS	79.33(5.83)	80.23(12.78)	0.813	59.00 (9.59)	80.24(12.94)	<0.001*	41.66 (18.76)	68.09(26.79)	<0.001*
Min, max	70, 90	60, 100		50, 80	60, 100		20, 80	20, 100
EORTC QLQ-C30
Global health status/QoL	67.77(8.39)	67.26(14.06)	0.831	58.05(9.15)	67.85(19.17)	0.010*	41.66(11.58)	65.27(27.16)	<0.001*
Functional scales
Physical functioning	84.00(12.81)	78.73(22.19)	0.541	60.22(17.19)	67.93(33.93)	0.096	26.66(25.37)	62.06(41.68)	0.002*
Role functioning	92.77(11.31)	86.11(18.73)	0.143	73.89(18.40)	74.60(32.35)	0.355	39.44(33.18)	66.26(40.73)	0.007*
Emotional functioning	76.94(14.79)	73.01(25.88)	0.831	75.55(12.36)	80.75(21.81)	0.035*	76.66(15.53)	85.11(18.90)	0.017*
Cognitive functioning	93.88(10.24)	86.50(16.14)	0.046*	86.66(12.68)	80.15(23.92)	0.459	62.22(25.86)	78.57(26.36)	0.007*
Social functioning	68.88(17.90)	75.00(22.16)	0.263	61.66(17.03)	76.54(23.89)	0.007*	48.33(24.89)	76.98(27.77)	<0.001*
Symptom scales
Fatigue	28.51(5.59)	33.86(25.02)	0.301	52.59(14.57)	29.36(26.06)	<0.001*	78.14(21.13)	27.77(33.22)	<0.001*
Nausea & vomiting	2.22(7.23)	8.53(18.85)	0.215	2.22(7.23)	4.36(15.20)	0.964	1.66(5.08)	2.38(11.38)	0.454
Pain	26.66(10.35)	28.57(23.07)	0.999	13.88(14.57)	21.42(21.55)	0.186	17.22(16.65)	17.85(16.20)	0.950
Dyspnea	7.77(14.33)	11.90(16.16)	0.236	18.88(16.79)	21.42(24.21)	0.839	37.77(24.34)	17.45(25.75)	0.004*
Insomnia	17.77(22.71)	32.53(33.03)	0.540	36.66(20.24)	20.63(23.22)	0.004*	50.55(27.85)	15.87(22.37)	<0.001*
Appetite loss	31.10(21.32)	30.15(20.57)	0.841	34.44(8.45)	23.80(25.80)	<0.001*	82.22(25.86)	22.22(27.21)	<0.001*
Constipation	16.66(16.95)	14.28(22.22)	0.364	43.33(19.86)	14.28(19.67)	<0.001*	81.11(24.26)	13.49(19.56)	<0.001*
Diarrhea	4.44(11.52)	5.55(14.56)	0.847	9.99(15.53)	6.34(15.15)	0.139	4.44(11.52)	3.96(10.92)	0.888
Financial difficulties	22.22(23.70)	26.19(28.06)	0.686	29.99(25.29)	24.60(26.60)	0.265	41.11(35.75)	23.01(27.03)	0.026*
EORTC QLQ- BIL 21
Eating scale	20.00(13.05)	25.00(20.82)	0.422	45.55(14.79)	25.79(20.14)	<0.001*	81.38(18.52)	33.72(28.80)	<0.001*
Jaundice scale	5.55(11.94)	8.20(10.71)	0.114	4.07(10.30)	8.99(14.14)	0.069	2.22(6.12)	9.78(18.39)	0.052
Tiredness scale	28.51(11.18)	26.45(24.77)	0.316	53.33(14.99)	29.09(27.32)	<0.001*	88.51(18.10)	34.12(32.22)	<0.001*
Pain scale	16.38(10.37)	19.04(14.98)	0.399	18.61(8.38)	18.25(16.38)	0.551	23.61(9.04)	19.64(19.36)	0.120
Anxiety scale	26.37(15.93)	35.91(26.89)	0.148	35.27(11.72)	32.53(26.21)	0.314	39.99(16.58)	32.73(27.38)	0.114
Treatment side-effects	29.99(20.24)	35.71(29.80)	0.426	26.66(16.14)	30.95(30.70)	0.854	16.66(20.99)	29.36(28.70)	0.63
Drainage bags/tubes	2.22(8.45)	4.76(13.91)	0.43	5.55(12.63)	7.14(15.67)	0.729	4.44(11.52)	9.52(19.87	0.452
Weight loss	21.11(16.33)	23.80(31.48)	0.674	41.10(14.34)	19.84(24.48)	<0.001*	72.22(19.73)	20.63(26.49)	<0.001*

* P value <0.05 were statistically significant.

Pre-treatment measures

At baseline, there were no statistically significant PPS, QoL, or symptom differences between the two groups on QLQ-C30, and QLQ-BIL21 except for higher cognitive functioning in the ST group over the CT group (p = 0.046).

All global health status and functional scores were >66, indicating higher QoL, while all symptom scores were moderate to low. Higher symptom scale scores indicate lower QoL.

Two-month follow-up

The CT group had statistically higher scores for both PPS and QoL than the ST group after 2 months (80.24 ± 12.97; 59.00 ± 9.59, p = 0.010).

In the functional domain, emotional and social function scores were also statistically significantly higher than for the CT group over the ST patients. The CT group now also had statistically significantly lower scores (better QoL) on 7 symptom scales: fatigue, insomnia, appetite loss, constipation, eating, tiredness and weight loss.

Four-month follow-up

Four months after treatment commenced the CT group again had statistically significantly higher PPS and QoL scores than the CT group (68.09 ± 26.79; 41.66 ± 18) (p < 0.010). Most notably, the CT group now also had significantly higher scores on all five Global Health Status QoL function scales: physical, role, emotional, cognitive and social functioning. The CT group also had statistically significantly lower scores (better QoL) on 8 symptom scales: fatigue, dyspnea, insomnia, appetite loss, constipation, eating, tiredness and weight loss.

Discussion

This study aimed primarily to compare health-related quality of life (HRQoL) between patients with advanced cholangiocarcinoma receiving standard palliative care (ST) versus those receiving medicinal cannabis treatment (CT). This is the first multi-center study in Thailand to explore this comparison in a real-world clinical setting. Although the two groups had similar HRQoL scores at baseline, the CT group consistently reported better global health status, functional outcomes, and lower symptom burden at the 2- and 4-month follow-ups.

To our knowledge, this is the first multi-center study comparing the effects of standard palliative care versus medicinal cannabis treatment on QoL on patients with advanced CCA. The two groups had little difference at baseline but at 2- and 4-month follow-ups the CT group consistently self-reported higher global health status and functional behaviors, and lower illness/symptom-related scores than the standard palliative-care group.

The CT regimen for our CCA patients was associated with meaningful improvements in health-related QoL consistent with previous improvements seen in pain reduction, quality of life, social life, and activity levels with other chronic pain patients.²⁸ From the second month of treatment our CT patients rated improvements in fatigue levels, insomnia, appetite loss, constipation, eating tiredness and weight loss. There was also a significant improvement in dyspnea at the fourth month, maybe due to cannabis’ beneficial effect on appetite, sleep and rest.²⁹ Other cannabis studies have shown more than 10% weight gain,³⁰ and cancer patients feeling refreshed, less fatigued and having reduced side-effects such as nausea, vomiting, and loss of appetite from treatment.³¹ Cannabinoids can also stimulate a therapeutic response via immune response enhancement.³² This is relevant due to current standard chemotherapy treatments which increase inflammation in all body systems with consequent intellectual impairments including attention, memory, decision making, risk management, fatigue, lack of motivation and peripheral nerve inflammation.³³ Cannabis or its derivatives have been widely used by patients with advanced cancer to help with cancer symptoms and treat side effects,³² and patients affirm its use for pain, anxiety, depression, and significantly prefer it over antianxiety medications.³⁴ It is also reported as useful for nausea, sleep, appetite stimulation,³⁴ and even at one-month follow-up, most parameters have been shown to improve significantly from baseline, including pain intensity, affective and sensory pain, sleep quality and duration, cancer distress, and both physical and psychological symptom burden.¹⁵

We found no inter-group differences in pain ratings between the second- and fourth-month follow-ups. Pain is one of most common symptoms associated with cancer,¹⁰ and is one of the symptoms patients fear most.¹¹ Unrelieved pain denies patients comfort and greatly affects their activities, motivation, social interactions, and overall quality of life.¹² Pain management goals are, therefore, is to reduce pain to a level that allows for an acceptable quality of life, and both CT and ST treatments appeared to do this satisfactorily. The benefit of pain relief must be balanced against the risk of adverse side-effects and overdose. Opioid analgesics are essential for the adequate treatment of moderate and severe cancer pain, however, despite good opioid control of baseline pain, some patients do have short-term, short-lived, intense pain episodes. A recent study on cannabis palliative care in oncology patients, had similar findings, suggesting that medical cannabis reduced chronic or neuropathic pain in advanced cancer patients¹¹ with significant improvements in other assessed parameters, including reduced pain intensity, improved sleep, and a decrease in pharmaceutical analgesics consumption.³³

There was no inter-group difference in anxiety ratings between the second- and fourth- month follow-ups for our patient groups. Anxiety is common in cancer patients and greatly influences survival rate, adherence to treatment, and quality of life. Advanced stage cancer patients, and those with metastasis, are more likely to have higher levels of anxiety than those with no sign of metastasis.³⁵ Some research on cannabis use in surviving cancer patients has found it alleviated 41.6% of anxiety symptoms,³⁶ however, research on cannabis use for anxiety and depression is currently limited, and there are many confounding factors. In addition, depression and anxiety are both normal and common responses to a cancer diagnosis, and therefore diagnosing clinical levels of anxiety and studying treatments to address these levels in the context of cancer is difficult.³⁷

In addition to quality-of-life outcome differences between ST and CT, research also shows a range of potential patient CT palliative-care access issues. Most patients need oncologist or primary care physician consultations. Thus, the primary care physician needs to be qualified and have good knowledge and a positive attitude towards the use of cannabis treatment among these patients. In an Australian study, most doctors felt their own knowledge was inadequate and only 28.8% felt comfortable discussing medicinal cannabis with patients. GPs generally rated their medical cannabis knowledge as poor and shared care arrangements with a specialist, though supported medical cannabis use in chronic cancer pain and palliative care.³⁸ Four themes were found to underpin reluctance to authorize medical cannabis in Canada; presumed lack of evidence, indications for therapeutic use, discomfort with therapeutic use and practitioner’s openness to emerging evidence.³⁹ Importantly, patients deciding to use cannabis to alleviate cancer symptoms, desired the approval from their medical team. While some patients found their physicians were willing to prescribe cannabis, or, refer them to a medical cannabis expert, some found their physicians were unwilling to discuss a cannabis option for managing their cancer symptoms⁴⁰ and, were not ready, or, did not want to answer patients’ questions about medical cannabis.⁴¹ Some clinicians feel hampered by a lack of clinically relevant information about cannabis use, efficacy, side-effects and have difficulty discussing the medicinal benefits of cannabis in a clinical settings.⁴² Another study found only 30% of oncologists felt sufficiently informed to make recommendations regarding medical cannabis treatment.²⁹

Most patients with advanced cancer experience symptoms throughout the disease trajectory, often with greater intensity as death approaches. If poorly managed, such symptoms can have a considerable impact on patients’ ability to function, their quality of life and ability to comply with anticancer treatments and use of health care resources.¹² Medical cannabis is another option to relieve symptoms caused by the cancer itself, direct or indirect consequences of the cancer, early or late adverse effects of treatment, and/or comorbid conditions cancer treatment, especially late stage cancer. Medical cannabis has been shown to relieve symptoms caused by cancer, to reduce chronic or neuropathic pain in advanced cancer patients⁴³ and to improve patients’ quality of life outcomes. Past medical cannabis treatment research evidence has been inconsistent and generally limited by poor quality, with large variations in cannabis-based products limiting the ability to make direct comparisons,⁴⁴ as well as studies lacking statistical power and with small subject sizes, and recommendations against the use of medical cannabis as a first or second line option for palliative cancer pain or when other treatments have failed.⁴⁵ Our study, found beneficial outcomes in a range of quality of life and symptom measures for cannabis treatment over standard palliative care protocols, using standardized medical cannabis products and treatment protocols.

This study has several limitations. One is the number of patients who dropped out before study completion likely due to rapid disease progression. Most patients were elderly and suffered from advanced CCA. Newly diagnosed CCA patients typically have a poor prognosis and short-term survival due to late-stage diagnosis. Registration for the standard palliative care clinic and/or cannabis clinic in each hospital also differs across physicians. Decision-making across patients, families, at different stages of disease, organ metastasis, and for methods of treatment also varies.

To the best of our knowledge, this is the first study to compare quality of life of CCA patients who received ST or CT and were monitored before treatment commencement and at 2 ^nd and 4 ^th month follow-ups and, across 8 hospitals, and 5 provinces. Medical cannabis products and usage was standardized under the Thai Food and Drug Administration regulations. The side effects, safety, benefits and harms of this cannabis have been reviewed and certified for patient treatment, by trained and Thai registered prescribers of medical cannabis.

Data availability

Underlying data

Figshare: QOL of patients with cholangiocarcinoma _ DATA, https://doi.org/10.6084/m9.figshare.17162621.v1.⁴⁶

Extended data

Figshare: QOL_document information, https://doi.org/10.6084/m9.figshare.17203922.v1.⁴⁷

This project contains the research information sheet.

Figshare: QOL_Inform consent, https://doi.org/10.6084/m9.figshare.17203931.v1.⁴⁸

This project contains the consent form.

Figshare: QOL_questionnaire, https://doi.org/10.6084/m9.figshare.17203934.v1.⁴⁹

This project contains the questionnaire.

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Acknowledgments

The authors would like to thank all patients and family colleagues in the Faculty of Medicine, Mahasarakham University especially the University Hospital Center of Excellence Team palliative clinic and cannabis clinic) for their invaluable help and encouragement throughout the course of this research. Finally, the authors express their appreciation for the participation of all patients in this research. This research project was financially supported by Mahasarakham University.

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48. Phansila N, Wongkongdech R, Sittiwet C: QOL_Inform consent. figshare. [Dataset]. 2021. Publisher Full Text
49. Phansila N, Wongkongdech R, Sittiwet C: QOL_questionnaire. figshare. [Dataset]. 2021. Publisher Full Text

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Version 2

VERSION 2 PUBLISHED 10 Jan 2022

Author details Author details

¹ Faculty of Medicine, Mahasarakham University, Mahasarakham, 44000, Thailand

Narisara Phansila
Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Writing – Original Draft Preparation

Chaiyasit Sittiwet
Roles: Conceptualization, Supervision

Ranee Wongkongdech
Roles: Conceptualization, Project Administration, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (2)

version 2

Revised

Published: 09 Apr 2025, 11:20

https://doi.org/10.12688/f1000research.75060.2

version 1

Published: 10 Jan 2022, 11:20

https://doi.org/10.12688/f1000research.75060.1

© 2025 Phansila N et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Phansila N, Sittiwet C and Wongkongdech R. Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand [version 2; peer review: 1 approved, 1 approved with reservations]. F1000Research 2025, 11:20 (https://doi.org/10.12688/f1000research.75060.2)

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Version 2

VERSION 2

PUBLISHED 09 Apr 2025

Revised

Views

Reviewer Report 29 May 2025

Budi Setiawan, Universitas Diponegoro/Dr. Kariadi Hospital, Semarang, Indonesia

Approved with Reservations

https://doi.org/10.5256/f1000research.180142.r385556

This study was eye opening, as medical cannabis was still a debate and this study have the potential as a reference regarding this regiment. However, there are still points I need to clarify.

Why did you

This study was eye opening, as medical cannabis was still a debate and this study have the potential as a reference regarding this regiment. However, there are still points I need to clarify.

Why did you employ a non-randomized sampling method? How did you make sure the sampling method would not add a bias?
What does the main regiment of the standard palliative care? Was there any detail regarding painkiller dose and regiment, and which patient received palliative chemotherapy and radiotherapy? I think those difference in palliative approach increase the risk of bias.
Can you better specify the dose and the regiment of cannabis of the cannabis group in your method / result?
There were some abbreviation that needed to be explained in their complete phrase, such ad THC, CBD, DTAM (method section).

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

Partly

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Hematology, Medical Oncology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Reviewer Report 26 Apr 2025

Ueamporn Summart, Faculty of Nursing,, Roi Et Rajabhat University, Selaphum, Roi Et, Thailand

Approved

https://doi.org/10.5256/f1000research.180142.r377012

CITE

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Author Response 25 Jun 2025

Narisara Phansila, Faculty of Medicine, Mahasarakham University, Mahasarakham, 44000, Thailand

25 Jun 2025

Author Response

Dear Reviewer,

On behalf of all co-authors, I would like to sincerely thank you for taking the time to review our revised manuscript titled "Comparison of effects of medicinal ... Continue reading Dear Reviewer,

On behalf of all co-authors, I would like to sincerely thank you for taking the time to review our revised manuscript titled "Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand."

We truly appreciate your valuable comments and suggestions, which greatly helped us improve the quality of our work. We are grateful for your final approval of our article, and we look forward to the opportunity to share our findings with a broader audience.

Thank you once again for your support and encouragement.

Best regards,
Dr.Narisara Pansila
Dear Reviewer,

On behalf of all co-authors, I would like to sincerely thank you for taking the time to review our revised manuscript titled "Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand."

We truly appreciate your valuable comments and suggestions, which greatly helped us improve the quality of our work. We are grateful for your final approval of our article, and we look forward to the opportunity to share our findings with a broader audience.

Thank you once again for your support and encouragement.

Best regards,
Dr.Narisara Pansila
Competing Interests: No competing interests were disclosed. Close
Report a concern
Author Response 24 Jun 2025

Narisara Phansila, Faculty of Medicine, Mahasarakham University, Mahasarakham, 44000, Thailand

24 Jun 2025

Author Response

Dear Reviewer,
Thank you very much for evaluating our revised manuscript and for your professional judgment indicating that the study meets an acceptable scientific standard.
We appreciate your support and ... Continue reading Dear Reviewer,
Thank you very much for evaluating our revised manuscript and for your professional judgment indicating that the study meets an acceptable scientific standard.
We appreciate your support and the opportunity to improve our work further. Should there be any additional suggestions or concerns in the future, we would be pleased to address them accordingly.
Sincerely,
Dr.Narisara Pansila
Dear Reviewer,
Thank you very much for evaluating our revised manuscript and for your professional judgment indicating that the study meets an acceptable scientific standard.
We appreciate your support and the opportunity to improve our work further. Should there be any additional suggestions or concerns in the future, we would be pleased to address them accordingly.
Sincerely,
Dr.Narisara Pansila
Competing Interests: No competing interests were disclosed. Close
Report a concern
Respond or Comment

COMMENTS ON THIS REPORT

Author Response 25 Jun 2025

Narisara Phansila, Faculty of Medicine, Mahasarakham University, Mahasarakham, 44000, Thailand

25 Jun 2025

Author Response

Dear Reviewer,

On behalf of all co-authors, I would like to sincerely thank you for taking the time to review our revised manuscript titled "Comparison of effects of medicinal ... Continue reading Dear Reviewer,

On behalf of all co-authors, I would like to sincerely thank you for taking the time to review our revised manuscript titled "Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand."

We truly appreciate your valuable comments and suggestions, which greatly helped us improve the quality of our work. We are grateful for your final approval of our article, and we look forward to the opportunity to share our findings with a broader audience.

Thank you once again for your support and encouragement.

Best regards,
Dr.Narisara Pansila
Dear Reviewer,

On behalf of all co-authors, I would like to sincerely thank you for taking the time to review our revised manuscript titled "Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand."

We truly appreciate your valuable comments and suggestions, which greatly helped us improve the quality of our work. We are grateful for your final approval of our article, and we look forward to the opportunity to share our findings with a broader audience.

Thank you once again for your support and encouragement.

Best regards,
Dr.Narisara Pansila
Competing Interests: No competing interests were disclosed. Close
Report a concern
Author Response 24 Jun 2025

Narisara Phansila, Faculty of Medicine, Mahasarakham University, Mahasarakham, 44000, Thailand

24 Jun 2025

Author Response

Dear Reviewer,
Thank you very much for evaluating our revised manuscript and for your professional judgment indicating that the study meets an acceptable scientific standard.
We appreciate your support and ... Continue reading Dear Reviewer,
Thank you very much for evaluating our revised manuscript and for your professional judgment indicating that the study meets an acceptable scientific standard.
We appreciate your support and the opportunity to improve our work further. Should there be any additional suggestions or concerns in the future, we would be pleased to address them accordingly.
Sincerely,
Dr.Narisara Pansila
Dear Reviewer,
Thank you very much for evaluating our revised manuscript and for your professional judgment indicating that the study meets an acceptable scientific standard.
We appreciate your support and the opportunity to improve our work further. Should there be any additional suggestions or concerns in the future, we would be pleased to address them accordingly.
Sincerely,
Dr.Narisara Pansila
Competing Interests: No competing interests were disclosed. Close
Report a concern

Version 1

VERSION 1

PUBLISHED 10 Jan 2022

Views

Reviewer Report 30 Jan 2024

Ueamporn Summart, Faculty of Nursing,, Roi Et Rajabhat University, Selaphum, Roi Et, Thailand

Approved with Reservations

https://doi.org/10.5256/f1000research.78877.r223474

Introduction:
1) What type of operation have you mentioned in this study? Please specify the survival rate of CCA patients (palliative or curative treatments) because the survival rate of curative resection is more than 1 year.
2) Paragraph 3: Please describe the association between pain, sleep, and HRQOL.
Methods :
1) For sample size calculation, what is the primary outcome of your study? Why you use the sample size for Bonferini's test?
2) Please describe more details about the standard treatment that the participants in both groups received.
3) Please identify some details about how the participants enrolled in both groups (including inclusion and exclusion criteria).
4) For the tool that is used to measure QOL, why does the author consider this tool? (as the specific QOL tool for CCA patients is FACT-HEP.)
4) Statistical analysis:
4.1) Please review the statistical analysis that you used to compare the primary outcome (HRQOL). Why does the author use non-parametric, given the low power of the test, instead of parametric? (following the results of assumption test ?)
4.2) For repeated measures more than twice, please avoid statistical testing more than once. I suggest that you can use the GEE ( the effect of dependency among observations that may cause ineffective and ineffective estimation of the parameter) and overestimate of the standard error (SE) for time-dependent covariates.
Results
1) Table 1 : Due to the imbalanced baseline characteristics of the participants ( such as gender), how can we solve this problem?
2) Table 2 : Show the mean scores between 2 groups that seem comparable. Why does the author use non-parametric instead of parametric so that you can show the magnitude of the effect (such as the mean difference)?
Discussion
Please review this part: I think the main objective of this study was to compare the mean scores of HRQOL between two groups

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

Partly

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Nursing and Biostatistics

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VERSION 2 PUBLISHED 10 Jan 2022

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Version 2 (revision) 09 Apr 25	read	read
Version 1 10 Jan 22	read

Ueamporn Summart, Roi Et Rajabhat University, Selaphum, Thailand
Budi Setiawan, Universitas Diponegoro/Dr. Kariadi Hospital, Semarang, Indonesia

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Reviewer Report

0 Views

29 May 2025 | for Version 2

Budi Setiawan, Universitas Diponegoro/Dr. Kariadi Hospital, Semarang, Indonesia

0 Views Cite this report Responses(0)

Approved With Reservations

This study was eye opening, as medical cannabis was still a debate and this study have the potential as a reference regarding this regiment. However, there are still points I need to clarify.

Why did you employ a non-randomized sampling method? How did you make sure the sampling method would not add a bias?
What does the main regiment of the standard palliative care? Was there any detail regarding painkiller dose and regiment, and which patient received palliative chemotherapy and radiotherapy? I think those difference in palliative approach increase the risk of bias.
Can you better specify the dose and the regiment of cannabis of the cannabis group in your method / result?
There were some abbreviation that needed to be explained in their complete phrase, such ad THC, CBD, DTAM (method section).

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

Partly

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Hematology, Medical Oncology

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Reviewer Report

8 Views

26 Apr 2025 | for Version 2

Ueamporn Summart, Faculty of Nursing,, Roi Et Rajabhat University, Selaphum, Roi Et, Thailand

8 Views Cite this report Responses(2)

Approved

I would like to thank you for making all the necessary changes and accepting the suggestions in this report. Most of my comments and limitations of this study have been clearly defined. In my opinion, I'm pleased to inform you that your manuscript has been deemed approved. Thank you for all of your efforts and time for improving all comments and suggestions.

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Nursing and Biostatistics

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

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Author Response

25 Jun 2025

Narisara Phansila, Faculty of Medicine, Mahasarakham University, Mahasarakham, 44000, Thailand

Dear Reviewer,

On behalf of all co-authors, I would like to sincerely thank you for taking the time to review our revised manuscript titled "Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand."

We truly appreciate your valuable comments and suggestions, which greatly helped us improve the quality of our work. We are grateful for your final approval of our article, and we look forward to the opportunity to share our findings with a broader audience.

Thank you once again for your support and encouragement.

Best regards,
Dr.Narisara Pansila

View more View less

Competing Interests

No competing interests were disclosed.

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Reviewer Report

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30 Jan 2024 | for Version 1

Ueamporn Summart, Faculty of Nursing,, Roi Et Rajabhat University, Selaphum, Roi Et, Thailand

13 Views Cite this report Responses(0)

Approved With Reservations

Is the work clearly and accurately presented and does it cite the current literature?

Yes
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

Partly

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Nursing and Biostatistics

Respond to this report

Responses (0)

Alongside their report, reviewers assign a status to the article:

Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions

[1] 1. Sripa B, Pairojkul C: Cholangiocarcinoma: Lessons from Thailand. Curr. Opin. Gastroenterol. 2008 May; 24(3): 349–356. PubMed Abstract | Publisher Full Text

[2] 2. Alsaleh M, Leftley Z, Barbera TA, et al.: Cholangiocarcinoma: a guide for the nonspecialist. Int. J. Gen. Med. 2018 Dec; 12: 13–23. PubMed Abstract | Publisher Full Text

[3] 3. Jansen H, Pape U-F, Utku N: A review of systemic therapy in biliary tract carcinoma. J. Gastrointest. Oncol. 2020 Aug [cited 2021 Nov 28]; 11(4): 770–789. PubMed Abstract | Publisher Full Text Reference Source

[4] 4. Mihalache F, Tantau M, Diaconu B, et al.: Survival and quality of life of cholangiocarcinoma patients: a prospective study over a 4 year period. J. Gastrointest. Liver Dis. JGLD. 2010 Sep; 19(3): 285–290.

[5] 5. Woradet S, Songserm N, Promthet S, et al.: Health-Related Quality of Life and Survival of Cholangiocarcinoma Patients in Northeastern Region of Thailand. PLoS One. 2016; 11(9): e0163448. PubMed Abstract | Publisher Full Text

[6] 6. Cai Y, Cheng N, Ye H, et al.: The current management of cholangiocarcinoma: A comparison of current guidelines. Biosci. Trends. 2016; 10(2): 92–102. PubMed Abstract | Publisher Full Text

[7] 7. WHO: WHOQOL User Manual: Programme on Mental Health. Geneva: World Health Organization; 1998. [cited 2021 Oct 22]. Reference Source

[8] 8. Chiu C-C, Lee K-T, Wang J-J, et al.: Preoperative Health-Related Quality of Life Predicts Minimal Clinically Important Difference and Survival after Surgical Resection of Hepatocellular Carcinoma. J. Clin. Med. 2019 Apr 27; 8(5): 576. PubMed Abstract | Publisher Full Text

[9] 9. Swarm RA, Paice JA, Anghelescu DL, et al.: Adult Cancer Pain, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2019 Aug 1; 17(8): 977–1007. PubMed Abstract | Publisher Full Text

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Comparison of effects of medicinal cannabis or standard palliative care on quality of life of patients with cholangiocarcinoma in Northeast Thailand

Abstract

Background

Methods

Results

Conclusions

Keywords

Revised Amendments from Version 1

Introduction

Study design and participants

Figure 1. Flow diagram of participants throughout the course of the study.

Participant enrollment and treatment procedures

Standard palliative care treatment

Medical cannabis treatment

Instrument and QoL assessment

Data collection and quality control

Data analysis

Ethical review

Results

Table 1. Participant characteristics (n = 72).

Table 2. Comparison of variables in European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30, QLQ- QLQ- BIL 21 (Pre-treatment, 2nd and 4th month treatment).

Pre-treatment measures

Two-month follow-up

Four-month follow-up

Discussion

Data availability

Underlying data

Extended data

Acknowledgments

References

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Table 2. Comparison of variables in European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30, QLQ- QLQ- BIL 21 (Pre-treatment, 2^nd and 4^th month treatment).