Bronchiolitis obliterans organizing pneumonia (BOOP) after thoracic radiotherapy for breast carcinoma

Common complications of thoracic radiotherapy include esophagitis and radiation pneumonitis. However, it is important to be aware of uncommon post-radiotherapy complications such as bronchiolitis obliterans organizing pneumonia (BOOP). We report on two patients with carcinoma of the breast who developed an interstitial lung disease consistent with BOOP. BOOP responds to treatment with corticosteroids and the prognosis is generally good despite of the need for long-term administration of corticosteroids as relapses can occur during tapering of steroids. This report provides guidelines for the evaluation and treatment of patients with pulmonary infiltrates after radiotherapy

Impact of the new rectal cancer definition on multimodality treatment and interhospital variability:Results from a nationwide cross-sectional study

Aim: This study aimed to determine the consequences of the new definition of rectal cancer for decision-making in multidisciplinary team meetings (MDT). The new definition of rectal cancer, the lower border of the tumour is located below the sigmoid take-off (STO), was implemented in the Dutch guideline in 2019 after an international Delphi consensus meeting to reduce interhospital variations. Method: All patients with rectal cancer according to the local MDT, who underwent resection in 2016 in the Netherlands were eligible for this nationwide collaborative cross-sectional study. MRI-images were rereviewed, and the tumours were classified as above or on/below the STO. Results: This study registered 3107 of the eligible 3178 patients (98%), of which 2784 patients had an evaluable MRI. In 314 patients, the tumour was located above the STO (11%), with interhospital variation between 0% and 36%. Based on TN-stage, 175 reclassified patients with colon cancer (6%) would have received different treatment (e.g., omitting neoadjuvant radiotherapy, candidate for adjuvant chemotherapy). Tumour location above the STO was independently associated with lower risk of 4-year locoregional recurrence (HR 0.529; p = 0.030) and higher 4-year overall survival (HR 0.732; p = 0.037) compared to location under the STO. Conclusion: By using the STO, 11% of the prior MDT-based diagnosis of rectal cancer were redefined as sigmoid cancer, with potential implications for multimodality treatment and prognostic value. Given the substantial interhospital variation in proportion of redefined cancers, the use of the STO will contribute to standardisation and comparability of outcomes in both daily practice and trial settings.</p

Prognostic significance of MRI-detected extramural venous invasion according to grade and response to neo-adjuvant treatment in locally advanced rectal cancer A national cohort study after radiologic training and reassessment

Background: Detection of grade 3–4 extra mural venous invasion (mrEMVI) on magnetic resonance imaging (MRI) is associated with an increased distant metastases (DM)-rate. This study aimed to determine the impact of different grades of mrEMVI and their disappearance after neoadjuvant therapy.Methods: A Dutch national retrospective cross-sectional study was conducted, including patients who underwent resection for rectal cancer in 2016 from 60/69 hospitals performing rectal surgery. Patients with a cT3-4 tumour ≤8 cm from the anorectal junction were selected and their MRI-scans were reassessed by trained abdominal radiologists. Positive mrEMVI grades (3 and 4) were analyzed in regard to 4-year local recurrence (LR), DM, disease-free survival (DFS) and overall survival (OS). Results: The 1213 included patients had a median follow-up of 48 months (IQR 30–54). Positive mrEMVI was present in 324 patients (27%); 161 had grade 3 and 163 had grade 4. A higher mrEMVI stage (grade 4 vs grade 3 vs no mrEMVI) increased LR-risk (21% vs 18% vs 7%, &lt;0.001) and DM-risk (49% vs 30% vs 21%, p &lt; 0.001) and decreased DFS (42% vs 55% vs 69%, p &lt; 0.001) and OS (62% vs 76% vs 81%, p &lt; 0.001), which remained independently associated in multivariable analysis. When mrEMVI had disappeared on restaging MRI, DM-rate was comparable to initial absence of mrEMVI (both 26%), whereas LR-rate remained high (22% vs 9%, p = 0.006). Conclusion: The negative oncological impact of mrEMVI on recurrence and survival rates was dependent on grading. Disappearance of mrEMVI on restaging MRI decreased the risk of DM, but not of LR.</p

Prognostic significance of MRI-detected extramural venous invasion according to grade and response to neo-adjuvant treatment in locally advanced rectal cancer A national cohort study after radiologic training and reassessment

Background: Detection of grade 3–4 extra mural venous invasion (mrEMVI) on magnetic resonance imaging (MRI) is associated with an increased distant metastases (DM)-rate. This study aimed to determine the impact of different grades of mrEMVI and their disappearance after neoadjuvant therapy.Methods: A Dutch national retrospective cross-sectional study was conducted, including patients who underwent resection for rectal cancer in 2016 from 60/69 hospitals performing rectal surgery. Patients with a cT3-4 tumour ≤8 cm from the anorectal junction were selected and their MRI-scans were reassessed by trained abdominal radiologists. Positive mrEMVI grades (3 and 4) were analyzed in regard to 4-year local recurrence (LR), DM, disease-free survival (DFS) and overall survival (OS). Results: The 1213 included patients had a median follow-up of 48 months (IQR 30–54). Positive mrEMVI was present in 324 patients (27%); 161 had grade 3 and 163 had grade 4. A higher mrEMVI stage (grade 4 vs grade 3 vs no mrEMVI) increased LR-risk (21% vs 18% vs 7%, &lt;0.001) and DM-risk (49% vs 30% vs 21%, p &lt; 0.001) and decreased DFS (42% vs 55% vs 69%, p &lt; 0.001) and OS (62% vs 76% vs 81%, p &lt; 0.001), which remained independently associated in multivariable analysis. When mrEMVI had disappeared on restaging MRI, DM-rate was comparable to initial absence of mrEMVI (both 26%), whereas LR-rate remained high (22% vs 9%, p = 0.006). Conclusion: The negative oncological impact of mrEMVI on recurrence and survival rates was dependent on grading. Disappearance of mrEMVI on restaging MRI decreased the risk of DM, but not of LR.</p

Prognostic Implications of Lateral Lymph Nodes in Rectal Cancer:A Population-Based Cross-sectional Study with Standardized Radiological Evaluation after Dedicated Training

BACKGROUND: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter, and location of lateral lymph nodes. OBJECTIVE: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI, and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training. DESIGN: Retrospective population-based cross-sectional study. SETTINGS: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals. PATIENTS: A total of 3057 patients underwent rectal cancer surgery in 2016: 1109 had a cT3-4 tumor located ≤8 cm from the anorectal junction, of whom 891 received neoadjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence and (ipsi) lateral local recurrence rates. RESULTS: Re-review identified 314 patients (35%) with visible lateral lymph nodes. Of these, 30 patients had either only long-stretched obturator (n = 13) or external iliac (n = 17) nodes, and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n = 284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (≥7 mm) lateral lymph nodes (n = 122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%; p &lt;.001) and lateral local recurrence (14.7%, 4.4%, 0%; p &lt; 0.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (HR 1.8 [1.1-2.8]) and enlarged lateral lymph nodes (HR 1.9 [1.1-3.5]) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year lateral local recurrence rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were found to be associated with higher univariate 4-year distant metastasis rates (36.4% vs 24.4%; p = 0.021), but this was not significant in multivariable analyses (HR 1.3 [0.9-1.]) and did not worsen overall survival. LIMITATIONS: This study was limited by the retrospective design and total number of patients with lateral lymph nodes. CONCLUSIONS: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without the prognostic impact of downsizing after neoadjuvant therapy. These results point toward the incorporation of primary lateral lymph node size into treatment planning. See Video Abstract.</p

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting

Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either ‘node-picking’ (the removal of an individual LLN) or ‘partial regional node dissection’ (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection. Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7–3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2–2.5, p = 0.874). Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.</p

Coverage of Lateral Lymph Nodes in Rectal Cancer Patients with Routine Radiation Therapy Practice and Associated Locoregional Recurrence Rates

Purpose: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for the occurrence of ipsilateral local recurrences (LLR) in rectal cancer. This study examined coverage of LLNs with routine radiation therapy practice in the Netherlands and associated LLR rates. Methods and Materials: Patients with a primary tumor ≤8 cm of the anorectal junction, cT3-4 stage, and at least 1 internal iliac or obturator LLN with short axis ≥5 mm who received neoadjuvant (chemo)radiation therapy, were selected from a national, cross-sectional study of patients with rectal cancer treated in the Netherlands in 2016. Magnetic resonance images and radiation therapy treatment plans were reviewed regarding segmented LLNs as gross tumor volume (GTV), location of LLNs within clinical target volume (CTV), and received proportion of the planned radiation therapy dose. Results: A total of 223 out of 3057 patients with at least 1 LLN ≥5 mm were selected. Of those, 180 (80.7%) LLNs were inside the CTV, of which 60 (33.3%) were segmented as GTV. Overall, 202 LLNs (90.6%) received ≥95% of the planned dose. Four-year LLR rates were not significantly higher for LLNs situated outside the CTV compared with those inside (4.0% vs 12.5%, P =.092) or when receiving &lt;95% versus ≥95% of the planned radiation therapy dose (7.1% vs 11.3%, P =.843), respectively. Two of 7 patients who received a dose escalation of 60 Gy developed an LLR (4-year LLR rate of 28.6%). Conclusions: This evaluation of routine radiation therapy practice showed that adequate coverage of LLNs was still associated with considerable 4-year LLR rates. Techniques resulting in better local control for patients with involved LLNs need to be explored further.</p

Prognostic Implications of Lateral Lymph Nodes in Rectal Cancer:A Population-Based Cross-Sectional Study with Standardized Radiological Evaluation after Dedicated Training

BACKGROUND: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter and location of lateral lymph nodes. OBJECTIVE: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training. DESIGN: Retrospective population-based cross-sectional study. SETTINGS: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals. PATIENTS: A total of 3057 patients underwent rectal cancer surgery in 2016: 1109 had cT3-4 tumor located =8?cm from the anorectal junction of which 890 received neoadjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence and ipsilateral local recurrence rates. RESULTS: Re-review identified 314 patients (35%) with visible lateral lymph nodes. 30 of these patients had either only long-stretched obturator (n = 13) or external iliac (n = 17) nodes and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n = 284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (=7?mm) lateral lymph nodes (n = 122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%, p &lt; .001) and lateral local recurrence (14.7%, 4.4%, 0%, p &lt; 0.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (hazard ratio 1.8 [1.1-2.8]) and enlarged lateral lymph nodes (hazard ratio 1.9 [1.1-3.5]) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year LLR rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were associated with higher univariate 4-year distant metastasis rates (36.4% 24.4%, p = 0.021), but not in multivariable analysis (hazard ratio 1.3 [0.9-1.]), and did not worsen overall survival. LIMITATIONS: This study was limited by the retrospective design and total number of patients with lateral lymph nodes. CONCLUSIONS: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without prognostic impact of downsizing after neoadjuvant therapy. These results point towards the incorporation of primary lateral lymph node size into treatment planning