Reduction of elective lymph node volume in radiotherapy of early anal squamous cell cancer: a comparative study between two Swedish university hospitals.

BACKGROUND: Anal squamous cell cancer (ASCC) in early stages (T1-2N0M0) is treated with chemoradiotherapy with a 3-year overall survival (OS) exceeding 90%. In Swedish guidelines, it has been optional to include the external iliac and presacral lymph node (LN) stations in radiotherapy (RT) treatment fields in early ASCC. Two Swedish hospitals treating ASCC (SU: Sahlgrenska University Hospital; UU: Uppsala University Hospital) have chosen different approaches since 2010. MATERIAL AND METHODS: This study included consecutive patients with early ASCC (T1-2N0M0) treated between 2010 and 2017 at both sites (SU n = 70; UU n = 46). Data were retrieved from medical records and RT charts. RESULTS: At SU, the external iliac and presacral LN stations were included in elective LN irradiation in 96.8% (n = 60) and 95.2% (n = 59) patients compared to 2.4% (n = 1) and 29.3% (n = 12) at UU. The mean elective LN volume was 2,313 cc (interquartile range [IQR] 1,951-2,627) in the SU cohort compared to 1,317 cc (IQR 1,192-1,528) in the UU cohort, p < 0.0001. No case of regional LN recurrence was seen in either cohort. Disease specific survival (DSS) at 5 years was 95.7% (confidence interval [CI] 90.1-100.0) in the SU cohort and 97.8% (CI 93.2-100.0) in the UU cohort (p 0.55). OS at 5 years was 84.5% (CI 76.1-93.0) in the SU cohort and 82.6% (CI 69.6-89.1) in the UU cohort (p 0.8). INTERPRETATION: We found no differences in regional recurrence, DSS or OS between the cohorts treated with different elective LN volumes. In this population-based study, reduction of RT volume in early ASCC did not lead to inferior outcome.

Doses to the right coronary artery and the left anterior descending coronary artery and death from ischemic heart disease after breast cancer radiotherapy: a case-control study in a population-based cohort.

BACKGROUND AND PURPOSE: Doses to the coronary arteries in breast cancer (BC) radiotherapy (RT) have been suggested to be a risk predictor of long-term cardiac toxicity after BC treatment. We investigated the dose-risk relationships between near maximum doses (Dmax) to the right coronary artery (RCA) and left anterior descending coronary artery (LAD) and ischemic heart disease (IHD) mortality after BC RT. PATIENTS AND METHODS: In a cohort of 2,813 women diagnosed with BC between 1958 and 1992 with a follow-up of at least 10 years, we identified 134 cases of death due to IHD 10-19 years after BC diagnosis. For each case, one control was selected within the cohort matched for age at diagnosis. 3D-volume and 3D-dose reconstructions were obtained from individual RT charts. We estimated the Dmax to the RCA and the LAD and the mean heart dose (MHD). We performed conditional logistic regression analysis comparing piecewise spline transformation and simple linear modeling for best fit. RESULTS: There was a linear dose-risk relationship for both the Dmax to the RCA (odds ratio [OR]/Gray [Gy] 1.03 [1.01-1.05]) and the LAD (OR/Gy 1.04 [1.02-1.06]) in a multivariable model. For MHD there was a linear dose-risk relationship (1,14 OR/Gy [1.08-1.19]. For all relationships, simple linear modelling was superior to spline transformations. INTERPRETATION: Doses to both the RCA and LAD are independent risk predictors of long-term cardiotoxicity after RT for BC In addition to the LAD, the RCA should be regarded as an organ at risk in RT planning.

Anal cancer in Sweden 2015-2019. Implementation of guidelines, structural changes, national registry and early results.

BACKGROUND: Squamous cell cancer of the anus is an uncommon malignancy, usually caused by human papilloma virus (HPV). Chemoradiotherapy (CRT) is the recommended treatment in localized disease with cure rates of 60-80%. Local failures should be considered for salvage surgery. With the purpose of improving and equalizing the anal cancer care in Sweden, a number of actions were taken between 2015 and 2017. The aim of this study was to describe the implementation of guidelines and organizational changes and to present early results from the first 5 years of the Swedish anal cancer registry (SACR). METHODS: The following were implemented: (1) the first national care program with treatment guidelines, (2) standardized care process, (3) centralization of CRT to four centers and salvage surgery to two centers, (4) weekly national multidisciplinary team meetings where all new cases are discussed, (5) the Swedish anal cancer registry (SACR) was started in 2015. RESULTS: The SACR included 912 patients with a diagnosis of anal cancer from 2015 to 2019, reaching a national coverage of 95%. We could show that guidelines issued in 2017 regarding staging procedures and radiotherapy dose modifications were rapidly implemented. At baseline 52% of patients had lymph node metastases and 9% had distant metastases. Out of all patients in the SACR 89% were treated with curative intent, most of them with CRT, after which 92% achieved a local complete remission and the estimated overall 3-year survival was 85%. CONCLUSIONS: This is the first report from the SACR, demonstrating rapid nation-wide implementation of guidelines and apparently good treatment outcome in patients with anal cancer in Sweden. The SACR will hopefully be a valuable source for future research.

Checkpoint Inhibition Causing Complete Remission of Metastatic Combined Hepatocellular-Cholangiocarcinoma after Hepatic Resection.

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer, speculated to arise from hepatic progenitor cells, and with a worse prognosis than hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) levels may be one prognostic factor. It has been suggested that checkpoint inhibition might be useful in the treatment of HCC where there is an increased expression of PD-1 and PD-L1 in the microenvironment. Its effect on CHC is unknown. We report a case with a large CHC, which was radically resected, but the 53-year-old female patient subsequently developed pulmonary metastases. Histology demonstrated low-differentiated CHC without microsatellite instability. Treatment with sorafenib was started but was stopped due to angioedema. Under subsequent gemcitabine/cisplatin treatment, the metastatic disease progressed with rising AFP levels. A third-line treatment with pembrolizumab was then started, 2 mg/kg b.w. i.v. every third week for 6 months. This resulted in a radiologically complete remission of the pulmonary metastases and AFP levels were normalized (<10 µg/L) from a level of 1,790 µg/L before treatment. The patient developed immune-related adverse events (AEs) including diarrhea and hepatitis. These AEs were successfully treated with prednisolone and mycophenolate mofetil, and they were eventually resolved. There are no signs of cancer recurrence neither in the liver nor in the lungs at 33 months after the start of the checkpoint inhibition treatment, and the patient is doing well. Further study is urgently needed on the role of checkpoint inhibition therapy in liver cancer.