Chapter 8 142 for patients with R0 resection it was 54 percent and only 32 percent for those with R1/ R2 resection (P = 0.012). Because the benefit of pathologic complete response was only apparent in the induction chemotherapy group, it might reflect a systemic effect reducing thedevelopment ofmicrometastases. Inductionchemotherapywas formerlyadministered exclusively topatientswithunresectable local recurrences, andeven intheseunfavourable cases the improvement in pCR and similar R0 rates are apparent. The findings in chapter 2 demonstrate that inductionchemotherapyhasadefiniterole in theneoadjuvant treatment of previously irradiated patients with locally recurrent rectal cancer. The study in chapter 3 investigated the effect of induction chemotherapy on pathologic complete response andclear resectionmargin rate inanextendedcohort andelaborates on the predictive value of pathological response. In this study, all patients with locally recurrent rectal cancer that underwent a resection after treatment with induction chemotherapy and (chemo)(re)irradiation, between 2010 and 2018, were included. This resulted in a cohort of 132 patients. Overall, a 17 percent pathological complete response rate was observed, resulting in an excellent 3-year overall survival of 92 percent. The degree of pathologic response was linearly correlated with the R0 resection rate (P = 0.026). In patients without synchronous metastases, pathologic response was an independent predictor for LRFS, MFS, and DFS (P = 0.004, P = 0.003, and P = 0.024, respectively), whereas R0 resection was an independent predictor for LRFS and OS (P = 0.020 and P = 0.028, respectively). Response to neoadjuvant treatment proves to be a powerful predictor of improved oncological outcome, underlining the importance of achieving a good response. An important subgroup of LRRC patients are those with a recurrence in the lateral lymph node compartment. It is hypothesised that local recurrence may arise from positive lymph nodes in the obturator compartment and around the iliac vessels. The extent and location of these local recurrencesmake surgical resection very challenging. In chapter 4 the treatment of these specific recurrences in the lateral compartment is evaluated. In total 51 patients were included with lateral local recurrences who underwent multimodality treatment. Thirteen (25 percent) of these patients were treated with induction chemotherapy, followed by chemo(re)irradiation and surgery. Major findings of this study were that induction chemotherapy resulted in high clear resectionmargin rate of 85 percent, whereas thiswas 45 percent in patientswho did not receive induction chemotherapy. Also, induction chemotherapy resulted in a pathologic complete response rate of 31 percent, compared with 8 percent for patients without induction chemotherapy. The 5-year local re-recurrence ratewas 64percent andoverall survival was 34 percent. Once again, analyses showed that the only factor improving survival rates was resection with clear margins. This study is limited by low patient
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