Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available.

Sung SY, et al. J Breast Cancer. 2020 Jun;23(3):291-302. https://doi.org/10.4048/jbc.2020.23.e30

Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.

We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.

Objective: Neoadjuvant chemoradiotherapy (CCRT) is current standards of care for locally advanced rectal cancer. The precise and thorough investigation of a tumor during the full course of CCRT by means of daily MRI can provide an idea on real-time treatment sensitivity in addition to tumor biology. Tumor volumetry from daily MRI during CCRT may allow patient-driven treatment decisions. Material and Methods: Patients diagnosed with cT3-4 and/or cN+ rectal adenocarcinoma undergoing preoperative CCRT with capecitabine on the pelvis up to 50 Gy in 25 daily fractions from November 2018 to June 2019 were consecutively included. Rectal tumor volume was uniformly measured by a single physician (YKK) in daily 0.35T MRI obtained with MR-guided linear accelerator. Primary endpoint was to assess the pattern of tumor volume regression throughout the full course of CCRT using daily registration MRI. Secondary endpoint was to assess the effect of tumor regression velocity on disease-free survival (DFS). Tumor regression velocity (cc) per fraction of each patient was calculated using the simple regression analysis of tumor volumes from fraction 1 to fraction 25. Results: Twenty patients were included. Daily tumor volumetry demonstrated linear tumor regression during CCRT. The tumor regression velocity of all 20 patients was 2.40 cc per fraction (R² = 0.93; p < 0.001). The median tumor regression velocity was 1.52 cc per fraction. Patients with tumor regression velocity ≥ 1.52 cc per fraction were grouped as rapid regressors (N = 9), and those with tumor regression velocity < 1.52 cc per fraction were grouped as slow regressors (N = 11). Rapid regressors had greater tumor regression velocity (4.58 cc per fraction) compared to that of slow regressors (0.78 cc per fraction) with statistical significance (p < 0.001). The mean DFS of rapid regressors was 36.8 months, numerically longer than the 31.9 months of slow regressors (p = 0.400) without statistical significance. Rapid regressors had numerically superior DFS rate compared to slow regressors without statistical significance. The 2-year DFS was 88.9% for rapid regressors and 72.7% for slow regressors, respectively (p = 0.400). Conclusion: This study is the first observation of linear tumor regression in daily MRI during the preoperative CCRT of locally advanced rectal cancer. Daily tumor regression velocity discriminated DFS, although without statistical significance. This study with a phenomenal approach is hypothesis-generating. Nevertheless, the potential of CCRT from therapeutics to a newer level, the “theranostics”, has been inceptively suggested. Further validation studies for the value of daily tumor volumetry on treatment decisions are warranted.