This study indicates that there may be differences in treatment and outcomes for patients with HGGs based on discharge location following resection. Compared to patients who were discharged home, patients who required any inpatient rehabilitation were found to have a longer LOS, longer WT, higher odds of excessive treatment delay, and shorter OS when examined separately. Although the median differences between AIRF and home discharge patients was minimal (32 days vs. 28 days), which may have little clinical significance, the fact that patients admitted to rehabilitation facilities have a much greater odds of an excessive delay in treatment is the most relevant to treatment timing in these patients. These results are consistent with our hypotheses: a longer LOS would be expected for these patients, as they must be evaluated by physical and occupational therapists, accepted to a rehabilitation program, and receive insurance approval prior to discharge [21]. Indeed, in this cohort, LOS was found to be significantly higher for patients evaluated by physical therapy independent of disposition (p < 0.0001). Longer LOS is associated with many well-known risks including hospital-acquired infections, increased overall mortality, and increased healthcare costs [22]. Additionally, as patients are often unable to receive cancer treatment until rehabilitation is complete, a longer WT would also be expected. In our experience, some rehabilitation facilities will not accept patients who are going to receive chemotherapy at all, and these patients are treated with radiation alone as a result. While this decision is in part based on the patient’s performance status, there is some bias based on insurance reimbursement policies. In addition to disposition, the discrepancy in OS could be due to a number of factors that have been shown to influence outcomes in HGG, such as functional status, that are not comprehensively explored [23–25].
While this study did not show an association between WT and OS, previous studies with robust analyses have demonstrated varying relationships [10, 12, 19, 26–32]. Pollom et al conducted a large retrospective cohort study of over 12,000 patients to evaluate the optimal timing of treatment initiation in GBM patients and discovered an inverse relationship between WT and OS particularly in patients who underwent gross total resection [28]. Unlike this study, Pollom et al. had a large sample size and created a model for assessing the relationship between WT and OS that controlled for several important prognostic factors, including age, sex, race, and comorbidity scoring. Recent studies that have not found a relationship between WT and OS have comparatively smaller sample sizes and/or fail to control for other prognostic factors [12, 26, 30, 31]. Naturally, there is concern that leaving such an aggressive tumor with a rapid doubling time untreated for several weeks could allow for further tumor growth [33]. Studies have shown increased contrast enhancement between the time of tumor resection and therapy initiation consistent with tumor progression in over 80% of patients, which is consistent with the imaging results found in this study [34]. Moreover, it has been shown that patients with radiological evidence of tumor progression prior to chemoradiation have decreased survival when compared to patients without evidence of tumor progression [35]. Due to ethical concerns, no prospective study has been designed to define the relationship between WT and prognosis. Despite the absence of conclusive data, the prospect of a delay in treatment of HGG can nevertheless serve as a source of anxiety for patients, family, and providers. However, in support of a generally accepted oncological principle, patients who are physically stronger before cancer treatment will survive longer. This is why other studies have shown that increasing a person’s physical strength before beginning intensive chemotherapy or radiation therapy can lead to better outcomes.
This study has several limitations. The single-institution, retrospective design has several disadvantages including the possibility of selection bias and questionable generalizability. Furthermore, the data that were collected were dependent upon prior recordkeeping and some factors that may have been informative in this analysis, such as functional status/comorbidity scoring and neurological status, were not consistently available. This study also had a relatively small number of rehabilitation patients that make it difficult to draw definitive conclusions about these populations. Lastly, in New York state, long term acute care facilities are not permitted, which limits the generalizability to other states whose post-acute care options are more available.
As the benefits of rehabilitation programs on the functional status, quality of life, and prognosis of patients with brain tumors have been well described [4–7, 9], it is important to identify any factors that may diminish these benefits or otherwise serve as a disincentive for optimal treatment of patients who may benefit from rehabilitation. Defining this disparity in treatment and outcomes is an essential first step in mitigating this discrepancy. This is especially true as patients who are discharged to rehabilitation locations often have worse functional status which is, in itself, a negative prognostic factor. Indeed, patients admitted to any rehabilitation facility in this cohort had older age and higher ASA scores than patients who were discharged home which also impact disease outcomes. Intraoperative implantation of carmustine wafers is a potential bridge therapy option for patients who are expected to have delayed treatment due to rehabilitation, though it is difficult to identify these patients pre-operatively. While this study is the first to provide evidence of treatment discrepancies based on discharge placements in HGG, more comprehensive, larger scale, multi-center studies should be conducted to corroborate these findings and minimize regional bias.