This retrospective study is the first to explicitly evaluate the impact of a pretherapeutic MTB presentation on patients with oral cavity cancer in terms of OS, DFS, 5-YS, and 5-YDFS. MTBs play a vital role in cancer treatment, particularly in specialized tumor centers. However, the existing evidence regarding a beneficial impact of MTB on patient survival and guideline adherence, especially in head and neck tumors, is limited.
This study focused exclusively on patients with oral cavity cancer, differentiating them from other head and neck cancers such as oropharyngeal, hypopharyngeal, laryngeal or salivary gland cancers (17, 18). This differentiation is crucial due to varying tumor characteristics and disease courses.
The cohort in this study included 630 patients with primary oral cavity cancer diagnoses. In comparison to previous single-center studies, which often included mixed head and neck cancer cases. Liu et al. included 224 HNSCC patients (13) and Rangabashyam et al. from 2020 included 221 patients with HNSCC (19). Furthermore, there have been a few multicenter studies, such as the one by Meltzer et al. including 3081 HNSCC patients (18) and Hansen et al. including 28293 HNSCC patients (20). These two studies encompassed all head and neck cancer sites. The largest studies examing the impact of MTB approaches in oral cavity cancer were conducted in Taiwan from Liao et al. 2016 including 1616 patients between 1996 and 2011 (21), and Tsai et al. as a nation-wide study in Taiwan with nearly 17000 patients (22).
This study employed a retrospective design, as was the case with many previous studies comparing patients treated pre- and post-implementation of MTBs (18, 20, 21). The groups of no-MTB and MTB presentation were predetermined due to the implementation of a MTB at the University Medical Centre Freiburg in 2014. To our knowledge, there is only one prospective study in the field of head and neck tumor treatment and MTB presentation, conducted by Wheless et al. (23). This study investigated changes in cancer classification and treatment regimen for malignant and benign head and tumors over three months (December 2009 - February 2010). 66% of the patients did not undergo change of diagnosis or treatment, whereas 27% of patients did had changes of diagnosis or treatment due to MTB presentation. The observed effect was stronger in malignant tumors with a change in treatment, mostly escalated due to the MTB presentation in 24% of the presented patients (23). Unfortunately, this study did not compare the treatment to local guidelines.
Tsai et al. performed a nationwide retrospective study on oral cavity cancer and postulated a beneficial impact of multidisciplinary treatment on OS (22). With a total of nearly 17000 patients this study offers a good overview on oral cavity cancer patients and performance in Taiwan. The study included patients from 2004–2010. UICC stages of oral cavity cancer were differentiated using the 6th UICC classification. This study revealed no significant improvement for OS in the stages I-III, with solely stage IV patients showing an improvement. This might indicate that center-based cancer treatment and MDT are particularly important in far advanced cancer stages and in treatment of highly difficult patients. However, the Taiwanese healthcare is not comparable to the situation in Germany, which is shown in the difference of the distribution of tumor stages among patient collectives. Compared to the study of Tsai et al. the percentage of patients with UICC IV stage was much lower in our study (51.6% vs. 31.6%, respectively). Furthermore, the study did not examine the influence of MTB on OS, instead it concentrated on the MDT. This is why the comparability between the study of Tsai et al. and ours is only partly reasonable.
The study by Friedland et al. found similar results to Tsai et collegues. Between 1996 and 2008 726 patients were included, having primary head and neck cancers. This study revealed significant improvement in 5-YSR in the stages I-III but a longer 5-YSR in UICC IV staged patients (17). Both studies did not evaluate the disease-free survival. Our study results align with the findings of Tsai et al. in stages I-III, as we observed no statistically significant improvement in 5-YS and 5-YDFS for those patients. UICC III patients in our study showed a tendency toward better 5-YS and 5-YDFS in the MTB group, although statistical significance was not achieved. However, unlike the other two studies, we did not recognize better 5-YS or 5-YDFS in UICC IV patients. Multivariate analysis in all UICC stages in our study failed to show an impact on the 5-YS and 5-YDFS.
In 2015 Liao et al. reported a higher 5-YSR for patients of all tumor stages of oral cavity cancer in the MTB group. Notably, their study included only primarily surgical treated patients (21), which differs from our study, where all patients were included, as in other previously mentioned studies (17, 20, 22). Liao et al. discussed the higher rate of neck dissections in the MTB group and higher rates of adjuvant radiotherapies in the MTB-group as possible factors for a better 5-YSR (21). It has been shown previously that neck dissection is a decisive factor in treatment of oral cavity cancer (24). This is crucial in comparing the data of Liao et al. with our study. Mandatory recommendations for neck dissections in Germany were implemented with the guideline in 2012, which resulting in most surgically treated patients undergoing neck dissection. This might explain the difference in survival data results between our study and Liao et al.’s.
Meltzer at al. published a retrospective study in 2021, including all head and neck cancer sites, showing a tendency towards a better 3-YSR and 3-YDFS for all stages, although statistical significance was not reached (18). Our data aligned with this tendency in UICC III stages. Meltzer et al. found an increase in the receipt of cisplatin-associated chemotherapy in the MTB group.
The retrospective study from 2020 by Hansen at al. showed a delay of treatment initiation of 18 days due to the MTB-associated approach (20). Our study observed a comparable delay of approximately 13 days across all UICC stages in the MTB group compared to the no-MTB group. The highest difference in TTI was seen in UICC I staged patients with a delay of over 13 days, followed by UICC IV staged patients with an 11-day delay. The data of Metzler at al. also aid our observation of 33.5 days TTI in the MTB group as they reported 32 days in the no-MTB group vs. 33 days in the MTB group (18). There is evidence, that TTI effects the outcome of patients with HNSCC (25, 26, 27). A longer TTI can be associated with a tumor progression between staging and treatment. This might result in clinical-to-pathological, which results in significantly poorer survival as described by Xiao et al. (28).
A recent study of Dayan et al. compared the time to initiation of postoperative radiation therapy and initial radiation therapy with prolonged time. Prolonged time to therapy was defined as > 42 days for initial radiotherapy and > 46 day for adjuvant radiotherapy. A significantly lower survival rate at 3 years was observed in the prolonged group of adjuvant radiotherapy (27). Rygalski et al. conduceted a retrospective study with over 37000 patients with HNSCC, showing a significant impact of delayed surgery on OS. The hazard ratio was increased the most 67 days after diagnosis, and an increase of hazard ratio of 4.7% was found for every additional 30 days of delay (25). Notably, the data published by Rygalski et al. were not specific to oral cavity carcinoma. However, the mean delay in our study was much lower than 67 days in both groups – those with and without MTB presentation. Taking this in consideration, the delay of approximately 13 days might not affect the OS or DFS.
A postulated goal of the MTB is to reduce TTI. This assumption was supported by a systematic review by Prades et al. in 2015 (11). Other beneficial side effects of the MTB, such as improving interdisciplinary work, providing a supervisory body, educating younger colleagues, and enhancing the quality of life through the interdisciplinary approach, are challenging to measure and were no part of the this study.
Nevertheless, our study found that the MTB presentation before treatment initiation lead to a higher level of coherence to the national guideline. This improvement was mainly evident in the group of UICC I patients, where 82.1% of the patients in the MTB group were treated according to the guideline, compared to 64.2% in the no-MTB group. This primarily involved resection with neck dissection, which was more frequently omitted in the no-MTB group. This resembles the findings of Liao at al. as described earlier (21).
As a retrospective study, there are several limitations in study design, data collection and potential sampling bias. It has been a single-center study, the results may be influenced by the surgical and medical skills of the physicians at the specific clinic. Aditionally, the introduction of the MTB could have resulted in a higher likelihood of the no-MTB group being treated before 2014, which could affect the measured overall survival in the two groups.