McCulloch M, Broffman M, van der Laan M, et al. Lung cancer survival with herbal medicine and vitamins in a whole-systems approach: ten-year follow-up data analyzed with marginal structural models and propensity score methods. Integr Cancer Ther. 2011 Aug 8. [Epub ahead of print]
A retrospective study comparing overall survival between short-term and long-term users of integrated cancer therapy and also against 2 external control groups.
All non-small-cell lung cancer (NSCLC) patients (n=239) presenting at a San Francisco Bay Area Chinese medicine center (Pine Street Clinic) from 1988 to 1993 who were also being treated at local oncology centers. Two external control groups of non-small cell lung cancer patients were obtained from the California Cancer Registry (CCR) and Kaiser Permanente Division of Research, Northern California (KPNC). All cases selected from the above databases were diagnosed with NSCLC between 1988 and 1993 to match the enrollment period of the clinical cohort.
Study Medication and Dosage
Pan-Asian medicine (PAM) plus vitamin (V) therapy. PAM treatment included dietary and lifestyle counseling, and herbal remedies. Acupuncture was provided on an as-needed basis. The vitamin therapy included various antioxidants, fish oil, and other nutraceuticals.
The Pine Street clinic participants were divided into 2 groups, short-term PAM+V and long-term PAM+V. The short-term group (SPAM+V) received treatment during active treatment only, whereas the long-term group (LPAM+V) continued treatment beyond the conclusion of chemotherapy.
Overall survival of SPAM+V compared to LPAM+V; overall survival of LPAM+V compared to the control databases
Of the 239 patients, 235 were included in the analysis: 181 LPAM+V subjects and 54 SPAM+V. The CCR provided data for 11,853 controls, and the KPNC provided data for 901 controls.
There was a statistically significant improvement in overall survival for LPAM+V versus SPAM+V in subjects with stages IIIB and IV NSCLC. The LPAM+V had 83% reduced risk of death in the Stage IIIB group and ~70% reduced risk in the Stage IV group compared to the SPAM+V group.
When compared to CRC controls, the LPAM+V had ~50% reduced risk of death in the Stage IIIA group and ~65% reduced risk in both Stages IIIB and IV groups. Compared to KPNC controls, LPAM+V had ~85% reduced risk in the Stage IIIA group, ~75% reduced risk in the Stage IIIB group, and ~80% reduced risk in the Stage IV group.
As seen from the table below, the absolute differences in survival rates were most dramatic at the first and second years after diagnosis.
Survival Rates at 1, 2, and 5 years from diagnosis of NSCLC
|LPAM +V||SPAM +V||CCR||KPNC|
|LPAM +V||SPAM +V||CCR||KPNC|
*Data reproduced from Table 7 of the study
Interestingly, the SPAM+V survival rates were relatively similar to the control groups at the respective years.
The study suggests a significant survival benefit in subjects diagnosed with later stage NSCLC when an integrative, whole-person approach was utilized long-term in comparison to short-term implementation and conventional therapy alone. Although this study provides a beginning foundation of information upon which to build future prospective studies, the conclusions drawn lose significance with further scrutiny.
The primary concern regarding the comparison between the Pine Street Clinic (PSC) subjects and the 2 external controls arises from the notable differences in conventional treatments received by the subjects. The PSC subjects in Stages IIIB and IV groups were more likely to receive chemotherapy than either external control group and less likely to have received radiation as the conventional treatment of their cancer. About 99% of PSC subjects in these two stages received chemotherapy and none received radiation. In comparison, about 30% of subjects in the external controls received chemotherapy and about 62% received radiation.
The study suggests that continued, not short-term, implementation of an integrative, holistic approach to cancer treatment confers a survival benefit.
Chemotherapy is now considered the treatment of choice for later-stage NSCLC. The fact that 65–70% of the control patients did not receive any chemotherapy would suggest an inherent treatment bias. The bias may be associated with different socioeconomic status and subsequent access to healthcare, as suggested by the authors. Regardless, the difference in treatment received precludes comparison of survival between the groups.
The intraclinic conclusions carry more weight because the above variables do not likely come into the equation. Though the number of subjects in the LPAM+V and SPAM+V groups is small, the differences in overall survival reached statistical significance. Unfortunately, no specific treatment information is provided to compare the subjects comprising the 2 PSC groups. Knowing the difference in the number of chemotherapy cycles received and total length of time patients received PAM+V treatment would provide important clinical information.
This information would provide insight into the chemo-responsiveness of the tumors within each treatment group. It is unclear whether the SPAM+V group had poorer survival because they discontinued the PAM+T treatment too early or if they had a more aggressive tumor, preventing them from continuing chemotherapy for an appreciable length of time before death.
Clinically, the study suggests that continued, not short-term, implementation of an integrative, holistic approach to cancer treatment confers a survival benefit principally at years 1 and 2 after diagnosis with NSCLC. Clearly the LPAM+V group had improved survival compared to controls, but it is unclear if this is due to the LPAM+V treatment, differences in conventional treatment, or other variables including selection bias and socioeconomic status. The patients presenting to the clinic likely had better socioeconomic status as they had adequate disposable income to sustain the out-of-pocket treatment regimen.
Outcomes data based on retrospective study design is inherently difficult to assess due to the number of potential variables when comparing 2 drastically different populations. This study contributes to the evidence that an integrated cancer treatment approach confers survival benefit to patients with NSCLC. As suggested by the authors, a prospective study would provide stronger evidence to guide clinical practice.
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