Reference ↗
Title	Lycopene in treatment of high-grade gliomas: A pilot study
Topic	Lycopene
Author	Puri, T, Goyal, S, Julka, PK, Nair, O, Sharma, DN, Rath, GK
Year	2010
Journal	Neurology India
DOI	https://doi.org/10.4103/0028-3886.60389

Brief summary

In this study, 50 patients with a high-grade glioma were treated with radiotherapy and concomitant chemotherapy for six weeks after surgery. One group of patients also received lycopene, the other group a placebo. The groups were comparable at the start of treatment. Six months after the intervention, the McDonald criteria were used to check how the development of the glioma had changed. More patients in the lycopene group tended to respond to the treatment and fewer patients showed progression. However, these differences between the groups could not be confirmed statistically (could not be distinguished from chance). This could have been due to the relatively small sample, as it is more difficult to prove an effect statistically in small samples, or to the fact that there was no relevant effect. No conclusions about the efficacy of lycopene can be drawn from this study.

In dieser Studie wurden 50 Patienten mit einem hochgradigen Gliom nach der OP sechs Wochen lang mit einer Radiotherapie und begleitender Chemotherapie behandelt. Eine Gruppe der Patienten hat zusätzlich Lycopin bekommen, die andere Gruppe einen Placebo. Die Gruppen waren zum Beginn der Behandlung vergleichbar. Sechs Monate nach der Intervention wurde anhand der McDonald Kriterien überprüft, wie sich die Entwicklung des Glioms verändert hat. Tendenziell sprachen mehr Patienten in der Lycopin-Gruppe auf das Treatment an und weniger Patienten hatten eine Progression zu verzeichnen. Diese Unterschiede zwischen den Gruppen konnten aber statistisch nicht bestätigt werden (nicht vom Zufall unterschieden werden). Das könnte an der relativ kleinen Stichprobe gelegen haben, da es in kleinen Stichproben schwieriger ist, einen Effekt auch statistisch nachzuweisen oder daran, dass es keinen relevanten Effekt gibt. Aus dieser Studie lassen sich keine Aussagen über die Wirksamkeit von Lycopin ableiten.

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies	Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Monocentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties	NI
Is randomized	Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control	No
Number of arms	2

Study characteristics

Inclusion criteria	Patients with high-grade gliomas (anaplastic astrocytoma or glioblastoma multiforme)
Exclusion criteria	NI
N randomized	50
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.	PP Analysis
Specifications on analyses	The data was analyzed using SPSS Software v10.0 (SPSS corporation Chicago IL) by applying Student’s t-test, ANOVA F test, Chi-square test and Karl Pearson Correlation Coefficient.
Countries of data collection	India
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T1: pre-radiotherapy T2: post-radiotherapy T3: 6 months after radiotherapy

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.	Adjuvant
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Brain and Central Nervous System (CNS) Cancers - High-Grade Glioma
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis	Advanced Stage
Specifications on cancer stages	NI
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	Concurrent chemotherapy with paclitaxel at a dose of 60 mg/m2i/v weekly
Previous cancer therapies	Surgery, Radiation therapy
Gender	Mixed
Gender specifications	Female n (%): 12 (24) Male n (%): 38 (76)
Age groups	Adults (18+)
Age groups specification	Age in years, mean (SD): 38.28 (14.07) Age in years, median (range): 38 (10-66)

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	25
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	1
Drop-out reasons	NI
Intervention	Lycopene + all patients received adjuvant radiotherapy and concurrent chemotherapy
Dosage and regime	8mg daily from day 1 of radiotherapy for 6 weeks
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	42
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Placebo
Number of participants (arm) N randomized	25
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	5
Drop-out reasons	NI
Intervention	Placebo + all patients received adjuvant radiotherapy and concurrent chemotherapy
Dosage and regime	From day 1 of radiotherapy for 6 weeks
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	42
Side effects / Interactions	NI

Outcomes

Tumor response

Outcome type As specificed by the authors	Primary
Outcome specification	Response rate: complete response (CR), partial response (PR), progressive desease (PD), stable desease (SD)
Type of measurement	McDonald criteria, MRI (Magnetic Resonance Imaging), SPECT (Single Photon Emission Computed Tomography)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NI
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Number of CR/PR/PD/SD/NA: no significant difference between arms (lycopene: 10/10/3/1/1, placebo: 5/6/8/1/5; p = 0.100, not significant)

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

PFS (Progression-Free Survival)

Outcome type As specificed by the authors	NI
Outcome specification	Time to progression
Type of measurement	Observation
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NI
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Mean value of weeks: no significant differences between arms (lycopene: 40.83, placebo: 26.74; p = 0.089, not significant)

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Funding and Conflicts of Interest

Funding	NI
Conflicts of Interest	According to authors no conflict of interest

Further points for assessing the study

Sample

Power analysis performed	?
- Sample size corresponds to power analysis	NI
- Reasons for insufficient sample size based on power analysis	NI
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	?
Ethnicity mentioned	?

Alternative Explanation

Other explanations for an effect besides the investigated intervention	NI
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing	NI
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over	NI
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?

Additional Notes