Differences between lung adenocarcinoma and squamous cell carcinoma in histological distribution of residual tumor after induction chemoradiotherapy

Aims To facilitate dose planning for convergent beam radiotherapy in non-small cell lung cancer (NSCLC), tumor response and histological distribution of residual tumors after induction chemoradiotherapy (ICRT) were compared between adenocarcinoma (AD) and squamous cell carcinoma (SQ). Methods Ninety-five patients with N1–2 or T3–4 NSCLC were treated with ICRT followed by surgery; 55 had AD and 40 had SQ. For the evaluation of distribution of residual tumors, the location of the external margin of residual tumors was assessed on surgical materials as follows: radius of whole tumor (“a”); distance between the center of tumor and the external margin of residual tumor (“b”); and its location (“b/a”). Results Of the 55 AD cases, 8 (15%) showed pathological complete remission, which was significantly less frequent than 22 of 40 SQ cases (55%) (p < 0.001). AD showed the residual tumors at the most periphery of tumor (b/a = 1.0) more frequently than SQ, i.e., 39/55 (71%) versus 6/40 (15%), respectively (p < 0.001). Even in 65 cases other than the pathological complete remission, external margins in 47 AD cases located more periphery than those in 18 SQ cases, of which mean b/a values were 0.97 ± 0.17 and 0.70 ± 0.29, respectively (p < 0.001). Conclusion AD showed worse tumor response to ICRT than SQ. After ICRT, AD remained at the periphery of primary tumor more frequently than SQ. It seems that, also in the convergent beam radiotherapy, the periphery part of AD would be more resistant than that of SQ.

Diffusion-weighted imaging or MR spectroscopy: Which to use for the assessment of the response to chemotherapy in breast cancer patients?

Background Diffusion-weighted MRI (DWI) and MR spectroscopy (MRS) both are noninvasive MR sequences that could be used as a reliable tool to assess the functional behavior of the breast cancer. The aim of the study was to assess the value of DWI and MRS in predicting the early response to neo-adjuvant chemotherapy (NAC) and absence of residual disease after treatment. Results One hundred thirty-three patients diagnosed with breast cancer and scheduled for NAC were enrolled in this study. All lesions were subjected to qualitative and quantitative analysis of DCE-MRI, DWI and MRS, where the lesions size, kinetic parameters, ADC values and MRS choline peak were recorded before the start of NAC and after completion of chemotherapy. The results of each MRI modality were correlated with the findings that were found at the pathology report of the complete surgical specimen. The sensitivity and specificity of the MR modalities to predict pathological complete remission post-NAC were 73.68% and 83.33%, respectively, using the kinetic curve pattern, 78.95% and 83.33%, respectively, using the ADC value and finally 78.95% and 91.67%, respectively, using the MRS choline peak. Similar sensitivity (89.47%) to predict pathological complete remission was presented by the ADC value and the MRS choline peak together when compared to the ADC value and dynamic curve patterns. Conclusion DWI and MRS are valuable MRI techniques and their accuracy in detecting residual disease is almost similar to that of DCE MRI. The inclusion of these sequences in the imaging protocol of NAC candidates improve monitoring of the response to treatment and allow early distinction between complete, partial and non-responders' cases in breast cancer patients.

Differences Between Lung Adenocarcinoma and Squamous Cell Carcinoma in Histological Distribution of Residual Tumor After Induction Chemoradiotherapy

Aims: To facilitate dose planning for convergent beam radiotherapy in non-small cell lung cancer (NSCLC), tumor response and histological distribution of residual tumors after induction chemoradiotherapy (ICRT) were compared between adenocarcinoma (AD) and squamous cell carcinoma (SQ). Methods: Ninety-five patients with N1-2 or T3-4 NSCLC were treated with ICRT followed by surgery; 55 had AD and 40 had SQ. For the evaluation of distribution of residual tumors, the location of the external margin of residual tumors was assessed on surgical materials as follows: radius of whole tumor (“a”); distance between the center of tumor and the external margin of residual tumor (“b”); and its location (“b/a”). Results: Of the 55 AD cases, 8 (15%) showed pathological complete remission, which was significantly less frequent than 22 of 40 SQ cases (55%) (p<0.001). AD showed the residual tumors at the most periphery of tumor (b/a=1.0) more frequently than SQ, i.e., 39/55 (71%) versus 6/40 (15%), respectively (p<0.001). Even in 65 cases other than the pathological complete remission, external margins in 47 AD cases located more periphery than those in 18 SQ cases, of which mean b/a values were 0.97 ± 0.17 and 0.70 ± 0.29, respectively (p < 0.001). Conclusion: AD showed worse tumor response to ICRT than SQ. After ICRT, AD remained at the periphery of primary tumor more frequently than SQ. It seems that, also in the convergent beam radiotherapy, the periphery part of AD would be more resistant than that of SQ.

Does pathological complete remission after neoadjuvant chemotherapy translate to longer relapse-free survival in patients with triple-negative breast cancer in the Indian population?

e12618 Background: Attainment of pathological complete remission (pCR) with neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) is associated with improved survival outcomes. However, data corroborating this fact is lacking from the Indian subcontinent. Methods: We evaluated 179 cases of TNBC, registered at Dr. B.R.A., I.R.C.H., AIIMS, New Delhi, from a period of May 2013 to July 2020, who were treated with neo-adjuvant chemotherapy (NACT) followed by surgery. Patients with oligometastatic disease who were treated with NACT with curative intent were also included in the analysis. Multivariate logistic regression analysis was done to explore the factors associated with the achievement of pCR. Survival analysis was done to study the correlation of pCR with relapse-free survival (RFS) and overall survival (OS). Results: The median age of our cohort was 43 (18-67) years. Study population comprised 104 (58.1%) pre-menopausal, 67 (37.4%) post-menopausal and 8(4.5%) peri-menopausal patients respectively. Twenty-three patients (12.9%) presented with early breast cancer, 144 (80.5%) were locally advanced and 12 (6.7%) were oligo-metastatic. Forty (22.4%), 127 (71.0%) and 12 (6.7%) patients were at clinical stages-II, III, and IV respectively at the time of presentation as per AJCC 7th edition. The median duration of symptoms was 4 (0.25-36) months. Forty-seven (26.3%) patients underwent breast conservation surgery and 128 (71.5%) patients had modified radical mastectomy. Overall pCR was attained in 29.6%(n=53) of the patients, with rates of 55%(n=22) and 23.6%(n=30) in patients with stage-II and stage-III respectively. Stage-II patients were more likely to achieve pCR after NACT [OR (95% CI: 4.3 (2.0-8.9)] when adjusted for other clinical covariates. Three-year RFS in patients achieving pCR was 94.7%, whereas in patients not achieving pCR was 43.9%, with a hazard of relapse or death significantly less in patients attaining pCR [HR (95% CI): 0.14 (0.06-0.37), p <0.0001]. Similarly, three-year OS was 97.4 % vs 73.8% in patients attaining pCR vs not attaining pCR, with a hazard of death significantly less in patients with pCR [HR (95% CI): 0.06 (0.01-0.45) p<0.006]. Conclusions: Our results confirm that attainment of pCR following NACT leads to better survival outcomes in TNBC. Factors associated with improved pCR rates in the Indian population needs further evaluation.

Residual Axillary Burden After Neoadjuvant Chemotherapy (NACT) in Early Breast Cancer in Patients with a priori Clinically Occult Nodal Metastases – a transSENTINA Analysis

Background Among patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), the association between pathological complete remission (pCR) in the breast and clinical/pathological parameters is well established, whereas the association between these parameters and residual axillary involvement after NACT remains unclear. Methods Patients with clinically occult nodal metastases (i.e. negative by clinical assessment but positive by SLNB prior to NACT, i.e. Arm B of the SENTINA trial) were included in the presented analysis. All patients received a second sentinel lymph node biopsy (SLNB) and axillary dissection after NACT. Univariate and multivariate analyses were carried out to evaluate the association between clinical/pathological parameters and axillary involvement after NACT. Results Arm B of the SENTINA study contained 360 patients, 318 of which were evaluable for this analysis. After NACT, 71/318 (22.3%) patients had involved SLNs or non-SLNs after NACT. Overall, 71/318 (22.3%) patients achieved a pCR in the breast. Associations of extranodal spread, lack of multifocality and pCR in the breast with residual axillary burden were statistically significant. In a descriptive analysis including all patients with clinically negative axilla before NACT in the SENTINA trial 1.2% of triple negative (TN) patients and 0.5% of HER/2 positive patients had residual axillary disease in case of a breast pCR. Conclusions Patients in the SENTINA trial with clinically negative axilla and involved SLNs still carried a significant risk of nodal metastases after NACT. However, the risk of residual axillary burden was particularly low in TN and HER/2 positive tumors in case of a breast pCR.

Perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2-positive resectable esophagogastric adenocarcinoma: Final results of the PETRARCA multicenter randomized phase II trial of the AIO.

4502 Background: Perioperative FLOT is a standard of care for resectable, esophagogastric adenocarcinoma (EGA). This trial evaluates the addition of trastuzumab (tras) and pertuzumab (per) to FLOT for HER2-positive resectable patients (pts). Methods: PETRARCA is a prospective, multicenter, randomized, investigator initiated trial planned as a phase II/III investigation. We report the phase II part of this trial. Pts with HER2+ resectable EGA (≥ cT2 or cN+) were enrolled. Pts were randomized 1:1 to 4 pre- and post-operative cycles of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m², q2w) (Arm A) or the same regimen with tras 8/6 mg/kg and per 840 mg q3w, followed by 9 cycles tras/per (arm B). Primary endpoint for the phase II part was the rate of pathological complete remission (pCR). Main secondary endpoints were DFS, OS and safety. Results: The trial closed prematurely and did not proceed to phase III. In total, 81 pts were randomized (A, 41; B, 40). Baseline characteristics were balanced (overall, male 79%; median age 60; cT3/T4 86%; cN+ 85%; GEJ 75%). 93% in arm A and 90% in arm B completed pre-OP treatment as planned. More pts had at least one dose modification in arm B (A, 44%; B, 70%). The pCR rate was significantly improved with tras/per (A, 12%; B, 35%; p = 0.02). Likewise, the rate of pathological lymph node negativity was higher with tras/per (A, 39%; B, 68%). R0-resection rate (A, 90%; B, 93%) and surgical morbidity (A: 43%; B, 44%) were comparable. Moreover, in-house mortality was equal in both arms (overall 2.5%). Median DFS was 26 months in arm A and not yet reached in arm B (HR 0.58, p = 0.14). After a median follow-up of 22 months median OS was not yet reached. DFS and OS rates [with 95% CI] at 24 months were 54% [38-71%] and 77% [63-90%] in arm A and 70% [55-85%] and 84% [72-96%] in arm B, respectively. In terms of toxicity more ≥ grade 3 adverse events were reported with tras/per (75% vs. 85%), especially diarrhea (5% vs. 41%) and leukopenia (13% vs 23%). Conclusions: The addition of tras/per to perioperative FLOT significantly improved pCR and nodal negativity rates in pts with Her2+ resectable esophagogastric adenocarcinoma at the price of higher rates of diarrhea and leukopenia. Clinical trial information: NCT02581462 .

Perioperative chemoimmunotherapy with durvalumab (Durva) in combination with cisplatin/gemcitabine (Cis/Gem) for operable muscle-invasive urothelial carcinoma (MIUC): Preplanned interim analysis of a single-arm phase II trial (SAKK 06/17).

499 Background: Cisplatin-based neoadjuvant chemotherapy followed by surgery is the standard of care for patients (pts) with MIUC but relapse rates remain high. Immune checkpoint inhibitors have demonstrated efficacy in advanced urothelial carcinoma (UC). We hypothesize that the integration of the PD-L1 inhibitor durvalumab into perioperative management of MIUC improves outcome. Methods: SAKK 06/17 is an open label single arm phase II study including 61 pts. Operable MIUC cT2-T4a cN0-1 pts without contraindication for Cis were eligible. Four cycles of preoperative Cis/Gem q3w are administered in combination with 4 cycles Durva 1500mg q3w starting at cycle 2. Durva is continued after surgery q4w for 10 cycles. Primary endpoint is event free survival at 2 years. We report a preplanned interim analysis of the secondary endpoints safety, pathological complete remission ypT0 N0 (pCR,) and pathological response rate (PaR, defined as ≤ypT1N0) on the first 30 resected pts. Results: Among 34 eligible pts (27M, 7F; median age 70, range 41-81 years) included from 07/18 – 02/19, 33 pts (97%) had primary bladder cancer and 1 pt had upper tract UC. Clinical T2, T3, T4 and TxN1 stage were present at diagnosis in 68%, 18%, 15% and 15%, respectively. Four cycles of chemo-immunotherapy were completed per protocol in 34 pts (100%). No tumor progression was noted at preoperative restaging. AE related to Durvalumab were G3 in 5 pts (15%) and G4 in 3 pts (9%). Surgery was performed as planned in 30 pts (88%), 3 pts refused surgery and 1 pt had a frozen pelvis. Operation technique was open in 20 pts (67%) and laparoscopic/robot-assisted in 10 pts (33%). Postoperative complications included Clavien-Dindo III in 6 pts (20%) and IV in 2 pts (7%) with infections being most common (5 pts, 17%). pCR was found in 9 pts (30%) and additional 6 pts (20%) had ypT1/ypTis for a PaR of 50%. Conclusions: The combination of Cis/Gem and Durva as neoadjuvant treatment for MIUC is feasible with manageable toxicities and pCR and PaR rates in the expected range. The rate of postoperative complications warrants further close follow up. Clinical trial information: 2017-003565-10.