ESTRO 2024 Congress report

The lower gastrointestinal (GI) 2 proffered papers nicely complemented the previous day's data, which covered results from the CAO/ARO/AIO-12 ("pick-the-winner") and RAPIDO trials or the use of new technologies such as proton therapy or MR-guided SBRT for rectal cancer.

ypN as a predictor for relapse in German randomised trials

Dr. Diefenhardt bridged the two sessions and discussed the findings from three German randomised trials (CAO/ARO/AIO-94, 04, and 12) involving 1888 patients undergoing neoadjuvant treatment. Of these patients, 29% (552) were found to have ypN1 or N2 lymph node metastases. The 5-year cumulative incidence of LRR (locoregional recurrence) was 3.4% for patients with ypN0, 6.3% for ypN1, and 16% for ypN2 (p<0.001). Similarly, the cumulative incidence of distant metastases at 5 years was 15% for ypN0, 39% for ypN1, and 65% for ypN2 (p<0.001). The 5-year overall survival rates were 86.1%, 74%, and 43% for patients in the respective groups (p<0.001). The natural question is whether there’s any role for treatment intensification with adjuvant chemotherapy in these groups, but the author underlines that prospective data does not unequivocally support this strategy.

Real-world data on the potential benefit of adjuvant chemotherapy

Picking up on this issue and highlighting the marked difference in using adjuvant chemotherapy for rectal cancer, Dr. Muirhead presented solid real-world data from England (2014-19) and the Netherlands (2012-17) on its potential benefit in curative patients who did not receive neoadjuvant chemotherapy. The presentation nicely underlined the differences between the two cohorts and a few things emerged: (1) when neoadjuvant chemoradiation was used, LCRT was the preferred treatment in England compared to the Netherlands (74% vs 54%), (2) adjuvant chemotherapy was more common in England (34.4% vs 3.6%) (3) adjuvant chemotherapy led to an increase in the 5-yr OS, which was statistically significant in the English Cohort, with those not receiving neo-adjuvant LCRT and those with high pathological stage receiving the most benefit.

To boost or not to boost?

On the same note, looking at ways of optimising LCRT, some interesting data emerged on a possible link to survival. Dr. Nicosia’s paper retrospectively assessed the role of EBRT boost (>54 Gy) in 800 LARC patients in whom it almost doubled the pCR rate (29.2% vs 16.1%), with T3-4 patients benefiting the most. However, this quadrupled both genitourinary (5.1% vs 1.4%, p=0.01) and acute gastrointestinal (6.3% vs 1.5%) toxicities, although actual numbers are low. The univariate analysis also showed that pCR correlated with a higher metastasis-free survival (5-year MFS of 77.5% vs 69.5%, p=0.03), but not OS (81.3% vs 75.2%, p=0.057). Another finding showed no pCR improvement after week 10 in the non-boost patients compared with those in the boost group, where tumour shrinkage continued.

Innovations in the neoadjuvant treatment for LARC-adaptive RT and combining chemoradiation with hyperthermia

The next presentations further introduced some fairly interesting ways of intensifying local treatment.

Dr. Passoni diligently built on the San Raffaele experience with preoperative adaptive radio-chemotherapy and presented the safety and efficacy of neoadjuvant oxaliplatin-based chemoradiation in 152 pts (2009-2023). While the results were comparable to the literature (locoregional relapse=3%, distant relapse=28%, median DFS and OS=105 and 133 months, respectively), the study’s materials and methods are fairly different from common practice, with a thorough, systematic radiobiological approach behind them. Suffice it to say that radiation was delivered in a dose of 41.4 Gy in 18 fr-2.3 Gy/fr for the first 12 fr and 3.1 Gy/fr for the last 6 fr, which integrated a mid-treatment adaptive boost (on a repeated pelvic MRI scan at half-treatment, i.e. after 9 fr).

Another unexpected method to optimise the treatment of LARC patients was presented by Dr. Risterer who spearheaded a multinational effort to understand the impact of combining chemoradiation with deep regional hyperthermia (HT). The thermal dose was expressed as cumulative equivalent minutes (CEM43). The acute overall toxicity≥G3 was 33% (51/153 available patients), with no G4 or G5 events. The pCR rate was 26%, while the LPFS, DFS, and OS were 93%, 67%, and 83%, respectively. The key message of the presentation was that “high” CEM43 (HT session≥3.5 min) was associated with better pCR compared to “low” CEM43 (HT session<3.5 min) in matched cohorts both with full method (28% vs 11%m p=0.01) and using nearest neighbour method (27% vs 11%, p=0.04).

While these were all commending efforts to improve treatment and avoid relapse, the final two presentations addressed the unfortunate locoregional and distant failure scenarios.

Guideline for the delineation of recurrent rectal cancer

Dr. Piqueur presented the effort to develop a consensus-based delineation guideline for locally recurrent rectal cancer (https://www.thegreenjournal.com/article/S0167-8140(22)04552-2/fulltext), which concluded that radiological support might reduce interobserver variability, especially in challenging situations such as fibrotic and anastomosis recurrences, or recurrences located in an abscess.

Fine-tuning SBRT for oligometastatic colorectal cancer

Finally, Dr. Stefanini's presentation ended the session with a philosophical touch to remind us that all is not lost even in the face of (oligo)metastatic disease, indeed especially in the face of (oligo)metastatic disease. Looking at 347 patients (mostly ECOG=0, 66.6%) with 820 treated oligometastases, the 1-yr, 3-yr, and 5-yr OS were 94.9%, 63.8%, and 45.1%, with a median OS of 51.6 months. Local control was also fair, with 79.4%, 67.8%, and 67.8%, respectively, with median LC not reached. Factors associated with poorer OS were a worse performance status and, interestingly, a lesion dimension greater than 14.1 cc. Meanwhile, more metastases and a BED<105.6 Gy were negative predictive factors for LC.

These were some of the promising ideas presented this year that nicely set the stage for the coming prospective studies. They underline that modern (Radiation) Oncology has the conceptual and technological ability to fight colorectal cancer on its own terms, to keep hope alive and resist till the heavy cavalry of the future arrives to lift the siege.

Tiberiu Popescu, MD

Radiation Oncologist

Amethyst RTC, Romania
Member of the ESTRO Lower GI Focus Group