The effect of examining somatic alterations with NGS in patients with solid tumors, on patient management: A single-center experience in Turkey.

OBJECTIVE: This study aimed to investigate the impact of analyzing somatic alterations using next-generation sequencing (NGS) on treatment management in patients with metastatic solid cancers and their ability to access NGS recommended treatments. METHODS: This retrospective study included eligible patients who underwent NGS on somatic tumor tissue. We examined the clinical and pathological characteristics of these patients and the alterations in their treatment following NGS results. RESULTS: A total of 101 patients who underwent NGS were included in the study. The most common cancers were non-small cell lung cancer (NSCLC), colorectal, and breast cancers, in that order. The median age was 58 (range 21-82) years, with 60 (59.4%) male participants. The median NGS turnaround time was 23 (range 17-29) days. NGS was performed on tissue from the primary lesion in 89(88%) patients. Predictive, prognostic, actionable, or variants of unknown significance were detected in 62(61.4%) patients. The most frequent variants identified were KRAS, EGFR, TP53, PIK3CA, and other rare mutations. Treatment was altered in 17(16.8%) patients based on NGS results. Of the 30 (29.7%) patients for whom NGS-informed treatment was recommended, only seven (6.9%) received the recommended therapy. There was no significant difference in overall survival (OS) between patients whose treatment was changed based on NGS results and those whose treatment remained unchanged (p = 0.897). There was no difference in OS between patients with and without variants (p = 0.384). CONCLUSIONS: NGS analysis of somatic alterations in patients with metastatic cancer may reveal additional variants beyond those identified by baseline tests. However, based on the recommendations of the reimbursement institution in Turkey, only a limited number of patients are able to access treatments recommended by NGS results. Therefore, baseline tests established in Turkey need to be made available in more centers in an appropriate time.

Prediction of the number of positive axillary lymph nodes according to sentinel lymph node involvement and biological subtypes in patients receiving neoadjuvant chemotherapy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for assessing axillary lymph node status in clinically node-negative breast cancer patients. However, the approach to axillary surgery after neoadjuvant treatment is still controversial. In the present study, our objective was to predict the pathological nodal stage based on SLNB results and the clinicopathological characteristics of patients who initially presented with clinical N1 positivity but whose disease status was converted to clinical N0 after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: After NAC, 150 clinically node-negative patients were included. The relationships between clinicopathologic parameters and the number of positive lymph nodes in SLNBs and ALNDs were assessed through binary/multivariate logistic regression analysis. RESULTS: Among 150 patients, 78 patients had negative SLNBs, and 72 patients had positive SLNBs. According to the ALND data of 21 patients with SLNB1+, there was no additional node involvement (80.8%), 1-2 lymph nodes were positive in 5 patients (19.2%), and no patient had ≥ 3 lymph nodes involved. Following the detection of SLNB1 + positivity, the rate of negative non-sentinel nodes were 75% in the luminal A/B subgroup, 100% in the HER-2-positive subgroup, and 100% in the triple-negative subgroup. Patients with a lower T stage (T1-3 vs. T4), fewer than 4 clinical nodes before NAC (< 4 vs. ≥4), and a decreased postoperative Ki-67 index (< 10% vs. stable/increase) were included. According to both univariate and multivariate analyses, being in the triple-negative or HER2-positive subgroup, compared to the luminal A/B subgroup (luminal A/B vs. HER2-positive/triple-negative), was found to be predictive of complete lymph node response. CONCLUSION: The number of SLNB-positive nodes, tumor-related parameters, and response to treatment may predict no additional nodes to be positive at ALND.

68Ga-FAPI PET/CT as an Alternative to 18F-FDG PET/CT in the Imaging of Invasive Lobular Breast Carcinoma.

Accurate staging of invasive lobular carcinoma (ILC), a subtype of breast cancer, is vital for effective clinical management. Although 18F-FDG PET/CT is a commonly used tool, its efficacy varies across different histologic subtypes. To mitigate this challenge, our investigation delves into the potential utility of 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT as an alternative for staging ILC, aiming to address a significant research gap using a more expansive patient cohort than the smaller samples commonly found in the existing literature. Methods: In this retrospective analysis, women diagnosed with primary ILC of the breast underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/CT. Both modalities were compared across all lesion locations with the used reference standard. The interval between scans was 1 wk, without any intervening treatments. Lesions were categorized visually, and tracer activity was analyzed using SUVmax, tumor-to-background uptake ratio, and uptake ratios. Both modalities were compared across various parameters, and statistical analysis was performed using SPSS 22.0. A P value of less than 0.05 was chosen to determine statistical significance. Results: The study included 23 female ILC patients (mean age, 51 y) with hormone-positive, human epidermal growth factor receptor type 2-negative tumors. Most (65%) had the luminal A subtype. 68Ga-FAPI PET/CT outperformed 18F-FDG PET/CT, with higher tumoral activity and tumor-to-background uptake ratios (P < 0.001). Primary tumors showed significantly increased uptake with 68Ga-FAPI PET/CT (P < 0.001), detecting additional foci, including multicentric cancer. Axillary lymph node metastases were more frequent and had higher uptake values with 68Ga-FAPI PET/CT (P = 0.012). Moreover, 68Ga-FAPI PET/CT identified more lesions, including bone and liver metastases. Pathologic features did not significantly correlate with imaging modalities, but a positive correlation was observed between peritumoral lymphocyte ratio and 68Ga-FAPI PET/CT-to-18F-FDG PET/CT uptake ratios (P = 0.026). Conclusion: This study underscores 68Ga-FAPI PET/CT's superiority over 18F-FDG PET/CT for ILC. 68Ga-FAPI PET/CT excels in detecting primary breast masses, axillary lymph nodes, and distant metastases; can complement 18F-FDG PET/CT in ILC; and holds potential as an alternative imaging method in future studies.

The Effectiveness of Adjuvant PD-1 Inhibitors in Patients With Surgically Resected Stage III/IV Acral Melanoma.

Our aim was to assess the efficacy of adjuvant programmed cell death protein-1 (PD-1) inhibitors and compare the other adjuvant treatments in patients with surgically resected stage III or IV acral melanoma. This study is a multicenter, retrospective analysis. We included 114 patients with stage III or IV acral malignant melanoma who underwent surgery within the past 10 years. We analyzed the effect of adjuvant programmed cell death protein-1 inhibitors on disease-free survival (DFS). The mean follow-up was 40 months, during which 69 (59.5%) patients experienced recurrence. Among the participants, 64 (56.1%) received systemic adjuvant therapy. Specifically, 48.4% received anti-PD-1 therapy, 29.7% received interferon, 14.1% received tezozolomide, and 7.8% received B-Raf proto-oncogene/mitogen-activated protein kinase inhibitors. Patients who received adjuvant therapy had a median DFS of 24 (10.9-37.2) months, whereas those who did not receive adjuvant therapy had a median DFS of 15 (9.8-20.2) months. Multivariate analysis for DFS revealed that the receipt of adjuvant therapy and lymph node metastasis stage were independent significant parameters ( P = 0.021, P = 0.018, respectively). No statistically significant difference was observed for DFS between programmed cell death protein-1 inhibitor treatment and other adjuvant treatments. Regarding overall survival (OS), patients who received adjuvant treatment had a median OS of 71 (30.4-111.7) months, whereas those who did not receive adjuvant treatment had a median OS of 38 (16.7-59.3; P = 0.023) months. In addition, there were no significant differences in OS observed between various adjuvant treatment agents ( P = 0.122). In our study, we have shown that adjuvant therapy had a positive effect on both DFS and OS in patients with stages III-IV acral melanoma who underwent curative intent surgery. Notably, we found no significant differences between anti-PD-1 therapy and other adjuvant therapies.

A perspective: the integration of ctDNA into Response Evaluation Criteria in Solid Tumours 1.1 for phase II immunotherapy clinical trials.

A consensus guideline, iRECIST, was developed by the Response Evaluation Criteria in Solid Tumours (RECIST) working group for the use of the modified RECIST version 1.1 in cancer immunotherapy trials. iRECIST was designed to separate pseudoprogression from real progression. However, this is not the only ambiguous situation. In clinical immunotherapy trials, stable disease may reflect three tumor responses, including real stable disease, progressive disease and responsive disease. The prediction of a "true complete/partial response" is also important. Much data has accumulated showing that ctDNA can guide decisions at this point; thus, integrating ctDNA into the RECIST 1.1 criteria may help to distinguish a true tumor response type earlier in patients treated with immunotherapy; however, prospectively designed validation studies are needed.

Lutetium-177-PSMA-617 radioligand therapy in patients with high volume metastatic prostate cancer prior to chemotherapy and new generation androgen deprivation therapy: Clinical Experience.

OBJECTIVE: We aimed to evaluate the efficacy oflutetium-177-prostate-specific membrane antigen-617 (177Lu-PSMA-617) with the luteinizing hormone releasing hormone (LHRH) analogues in the first or in the second-line setting formetastatic castration sensitive patients and metastatic castration resistance after progression with LHRH analogues. SUBJECTS AND METHODS: Sixteen consecutive patients with high volume metastatic prostate cancer undergone 177Lu-PSMA-617 therapy who were refused chemotherapy and were unable to use new generation anti-androgen drugs because of unavailibility of reimbursement, were included in this retrospective study. Prostate specific antigen (PSA) response (>50% decrease), disease control rate (DCR: complete or partial response), progression-free survival (PFS) and overall survival (OS) were calculated to evaluate according to the clinicopathological features of the patients. Treatment response evaluated by 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT). RESULTS: Mean age was 74,6 (SD±8,36). Among them, 7 (43,8%) patients has castration resistant disease, while the remaining has castration sensitive disease. Lutetium-177-PSMA-617 was administered to 10 (62,5%) patients as one of the first-line treatment and 6 patients received the treatment after progression on LHRH as a second-line treatment. Considering all patients, PSA response rate and DCR were 50% and 62% respectively. The median PFS and OS (with 95% CI) were 11,2 months (11-15) and 29 months (25,6-32,4), respectively in patients treated with 177Lu-PSMA-617 and LHRH analogues. Clinicopathological features and basal PSA level did not have effect on PSA response rates, DCR, OS and PFS. On the other hand, increment in PFS and OS (with 95% CI) was observed in castration resistant disease and in the second-line therapy; for castration resistant disease 16,5 months (12.3-19.7); 30 months (25.3-32.7), for the second-line therapy 14.5 months (12-20.5); 29 months (NR), respectively but statistically not significant. Serious toxicity was observed in a limited number of patients (18,7%), treatment-related death was not observed. CONCLUSION: Favorable results can be achived with second-line 177Lu-PSMA-617 treatment in terms of OS and PFS, especially in castration-resistant disease, when chemotherapy and new generation ADT's cannot be used.

Should We Completely Exclude Locoregional Therapy for the Primary Tumor from Our Clinical Practice in De Novo Metastatic Breast Cancer?

Locoregional therapy (LRT) for the primary site of breast cancer (BC) is one of the most debated topics in de novo metastatic disease. We have four main randomized controlled trials, three negative and one positive, together with one positive prospectively designed non-randomized study investigating the contribution of LRT to the literature. We aimed to discuss the possible reasons for the positive or negative results of the studies and to identify specific subgroups that may benefit from primary breast surgery.

The predictive value of vitamin D follow-up and supplementation on recurrence in patients with colorectal cancer.

Aim: Vitamin D has a role in carcinogenesis and may have effect on recurrence. Thus, we aim to analyze the prognostic effect of vitamin D levels at beginning and follow-up together with the contribution of vitamin D supplementation on patients with colorectal cancer (CRC). Materials & methods: CRC patients who underwent curative surgery were included. Patients' vitamin D values were assessed under four groups according to baseline and follow-up vitamin D values, and whether vitamin D supplementation was used. Survival distributions were compared for vitamin D groups. Results: Patients with a high follow-up vitamin D level and a high vitamin D level after supplementation presented with better disease-free survival and overall survival than patients with low vitamin D and low vitamin D levels after supplementation. Conclusion: Follow-up vitamin D values seems to be a good predictive biomarker and vitamin D supplementation may have a positive effect on survival.

Comparison of 68Ga-FAPI PET/CT and 18FDG PET/CT Modalities in Gastrointestinal System Malignancies with Peritoneal Involvement.

PURPOSE: In this study, we aimed to investigate the utilization of 68Ga-FAPI PET/CT in comparison to 18FDG PET/CT to evaluate the peritoneal involvement of the gastrointestinal malignancies alongside primary lesions and other metastatic foci. PROCEDURES: A total of 37 patients with various gastrointestinal malignancies with accompanying peritoneal involvement who underwent 68Ga-FAPI PET/CT and 18FDG PET/CT imaging between September 2020 and June 2021 were included in this retrospective study. SUVmax values of 68Ga-FAPI and 18FDG were compared according to lesion locations. Also, the lesion localization ability of both imaging was compared in patient basis. RESULTS: Of the 37 patients with peritoneal involvement (23 males and 14 females; median age, 62.8 ± 12.7 years), 35.1% (n = 13) had colorectal cancer, 37.8% (n = 14) gastric cancer, and 27.0% (n = 10) pancreaticobiliary cancer. While 45.9% of them were operated, the remaining did not have surgery. The mean time interval between two studies was 3.2 days (range: 2-6 days). The mean SUVmax value of peritoneal metastases (p < 0.001) was significantly higher with 68Ga-FAPI PET/CT compared to that with 18FDG PET/CT, as in primary lesions (p < 0.001), lymph node metastases (p = 0.006), liver metastases (p = 0.002), and bone metastases (p = 0.018). A total of 185 lesions was detected in the initial assessment with 18FDG PET/CT. Of the total lesions detected with 18FDG PET/CT, 5 of them were evaluated as benign lesions with 68Ga-FAPI PET/CT also in accordance with the reference standard. In addition to 180 lesions detected with 18FDG PET/CT, a total of 37 additional malignant lesions, 12 of which were peritoneal metastases, were detected with 68Ga-FAPI PET/CT. CONCLUSION: 68Ga-FAPI PET/CT was determined to be superior to 18FDG PET/CT in terms of detection of peritoneal involvement with high image quality as well as primary tumor and other metastatic foci. Consequently, 68Ga-FAPI PET/CT can be used as a complementary imaging modality especially for inconclusive 18FDG findings due to the lack of accuracy of 18FDG PET/CT in some of the metastatic regions, especially in the liver.

Dramatic response to crizotinib in a breast cancer patient with ALK gene rearrangement.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3-5% of non-small-cell lung cancer (NSCLC), while it was 0.2% in NSCLC tumors. Due to its low frequency, it is extremely challenging to conduct randomized clinical trials of ALK-targeted therapies in NSCLC tumors. In the present case, we describe the first reported case of triple-negative breast cancer (TNBC) harboring the ALK fusion mutation that responded to ALK-targeted therapy after progression with two lines of chemotherapy. Searching for ALK gene rearrangement or other fusion, especially in patients with chemotherapy-resistant TNBC, opens the door to new treatment strategies.

Comparison of [68Ga]-FAPI PET/CT and [18F]-FDG PET/CT in Multiple Myeloma: Clinical Experience.

OBJECTIVE: In this study, we aimed to compare [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging to detect lesions in multiple myeloma. METHODS: A total of 14 patients with multiple myeloma who underwent [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging were included in this retrospective study. SUVmax values of [68Ga]FAPI and [18F]FDG were compared according to lesion locations. Also, lesion localization ability of both imaging methods was compared on the patient basis. RESULTS: In 4 of 14 patients, [68Ga]FAPI PET/CT and [18F]FDG PET/CT have not detected any bone lesions. In 8 of the remaining 10 patients [18F]FDG PET/CT detected bone lesions but in this group, 6 patients showed more higher SUVmax values than [18F]FDG PET/CT in [68Ga]FAPI PET/CT.In contrast, 2 of 8 patients showed more higher SUVmax values than [68Ga]FAPI PET/CT in [18F]FDG PET/CT. Moreover, [68Ga]FAPI PET/CT detected bone lesions in two patients, which werenot detected by [18F]FDG PET/CT. Also, in five patients, [68Ga]FAPI PET/CT showed more bone lesions in comparison with[18F]FDG PET/CT. Only one patient, [18F]FDG PET/CT showed more bone lesions. Three extramedullary involvements were observed in the following locations: lung, presacral lymph node, and soft tissue mass lateral to the right maxillary sinus. Among these involvements, higher SUVmax values were observed in the lung and presacral lymph node with [68Ga]FAPI compared to [18F]FDG. However, the soft tissue mass showed a higher SUVmax value in [18F]FDG than [68Ga]FAPI. CONCLUSIONS: No significant superiority was observed in [68Ga]FAPI PET/CT over [18F]FDG PET/CT in patients with MM. However, [68Ga]FAPI PET/CT can be utilized as a complementary imaging method to [18F]FDG PET/CT in some settings, especially in low-[18F]FDG affinity and inconclusive cases. Considering the favorable aspects of [68Ga]FAPI PET/CT in MM, such as low background activity, absence of non-specific bone marrow, and physiological brain involvement, further studies with a larger sample size should be conducted.

Superiority of 68Ga-FAPI PET/CT scan in detecting additional lesions compared to 18FDG PET/CT scan in breast cancer.

PURPOSE: We compared the ability of 68Ga-FAPI PET//CT with 18FDG PET/CT imaging techniques to detect additional lesions in breast cancer patients that may affect further chemotherapy options. METHODS: A total of 48 patients with breast cancer underwent concurrent 68Ga-FAPI-04 and 18FDG PET/CT regardless of whether they had received chemotherapy or not in the last month before imaging. Both modalities were compared according to various parameters: clinical/pathological features, number of lesions detected, activity uptake (SUVmax), and the effect on the evaluation of response to treatment in the post-chemotherapy group. RESULTS: This retrospective study included 48 patients with breast cancer (mean age 53.3 ± 11.7 years; IDC 89.6%; ILC 10.4%). In the comparison of both modalities, no statistical significance was obtained in terms of the pathological characteristics of the patients. More lesions were demonstrated in all categorized regions in 68Ga-FAPI PET/CT imaging with higher uptake values compared to 18FDG PET/CT in this study. In the treatment response evaluation of the post-chemotherapy group, 12 cases (12/24) who were evaluated as PMR, CMR, or SD according to 18FDG PET/CT results were later accepted as PD due to newly detected lesions in complementary 68Ga-FAPI PET/CT imaging and treatment of patients was managed accordingly by clinicians. CONCLUSION: It was determined that 68Ga-FAPI PET/CT was superior to 18FDG PET/CT in terms of accuracy and it was thought that 68Ga-FAPI PET/CT could be utilized as an additional complementary imaging to 18FDG PET/CT. Moreover, 68Ga-FAPI PET/CT, with its significant theranostic potential, could become a key element in predicting the pathological response of breast cancer patients in further researches.

Association of illness perception with chemotherapy-induced nausea and vomiting: a Turkish Oncology Group (TOG) study.

Chemotherapy-induced nausea and vomiting (CINV) may be linked to the psychological status of cancer patients. Therefore, the authors aimed to better understand the underlying risk factors for CINV using the Brief Illness Perception Questionnaire. A total of 238 patients were recruited during three cycles of chemotherapy. Patient, disease and treatment characteristics were noted at the onset of chemotherapy. The Brief Illness Perception Questionnaire was administered face-to-face prior to chemotherapy. The relationship between illness perceptions and CINV was analyzed using Spearman's rank correlation. Positive illness perception parameters, including personal and treatment control, were negatively correlated, whereas negative illness perception parameters, including consequences, timeline, identity, concern and emotions, were positively correlated with CINV after adjusting for age, sex and emetogenic potential of chemotherapy (p < 0.001). Illness perception may be an underlying risk factor for CINV.

Prediction of Peritoneal Recurrence in Patients with Gastric Cancer: a Multicenter Study.

PURPOSE: The peritoneum is the common recurrence site of gastric cancer (GC) presenting with worse survival. Although some predictive clinicopathological factors have been identified, there is no comprehensive assessment of peritoneal recurrence risk prediction for patients treated with adjuvant chemotherapy (CR) or chemoradiotherapy (CRT) after surgery. We aimed to predict peritoneal recurrence and develop a new scoring model in GC. METHODS: This retrospective study included 274 GC patients who presented with recurrence after curative gastrectomy followed by adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). Risk factors for peritoneal recurrence were analyzed using the following parameters: age, gender, tumor location and characteristics, and differences between treatment modalities. All parameters were assessed by binary logistic regression analysis to compare the patients with and without peritoneal recurrence. Then, a new risk scoring model was developed. RESULTS: Peritoneal recurrence was observed in 115 (44.1%) patients. Peritoneal recurrence was higher in female gender (odds ratio (OR), 1.93; 1.07-3.49, P = 0.030, 1 point), T4a-b stage (OR, 2.47; 1.14-5.36, P = 0.022, 1 point), poor/undifferentiated (OR, 2.04; 1.31-4.06, P = 0.004, 1 point), and signet cell carcinoma (OR, 2.04; 1.04-4.02, P = 0.038, 1 point) after adjusted for resection and dissection types. The risk scoring model was developed using the related parameters: Peritoneal recurrence rates were 24.6%, 42.6%, and 71.4% for group 1 (0 point), group 2 (1-2 points), and group 3 (3-4 points), respectively. CONCLUSION: Female gender, T4 tumor stage, undifferentiated histopathology, and signet cell type had a tendency to peritoneal recurrence after adjusted for treatment modalities. Patients with 3 or 4 risk factors had an 8.8-fold increased risk for the development of peritoneal recurrence.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.

Recurrence pattern in the presence of hepatosteatosis in breast cancer: does it facilitate liver metastasis?

Aim: We aimed to investigate the impact of hepatosteatosis (HS) severity on the recurrence pattern of breast cancer and to clarify whether HS causes affinity to recurrence with liver metastasis. Materials & methods: The median follow-up was 80.0 (4-217) months and the mean age was 47.9 ± 11.3 years. Among all, 181 (39.9%) patients were diagnosed with grades 2 and 3 HS. Of total, 158 (34.8%) patients have experienced recurrence. Results: While higher degree of HS was more common in patients presented with liver recurrence (odds ratio; 95% CI: 2.50; 1.27-4.92; p = 0.007), it was lesser in those with other metastatic sites (all were >0.05). Liver-recurrence-free survival was significantly worse in the group with higher degree of HS (hazard ratio; 95% CI: 2.46; 1.4-4.3; p = 0.002) together with younger age (hazard ratio; 95% CI: 2.44; 1.4-4.3; p = 0.002) in multivariate analysis. Conclusion: HS might have produced an affinity for liver metastasis in common types of breast cancer patients in remission independent from metabolic disorders or clinicopathologic features.