Tumor Restaging Research Articles

The NEO-RT trial: A phase 3 randomized trial of neoadjuvant chemotherapy, excision and observation versus chemoradiotherapy for early rectal cancer, CCTG CO.32.

TPS3646 Background: There is significant interest in organ-sparing management of rectal cancer. Data from the National Cancer Database suggest that in 2020 only 20% of US patients with stage I rectal cancer are managed non-operatively. The phase II CCTG CO.28/NEO trial previously reported high rates of tumor downstaging, organ preservation and excellent rectal function among patients with T1-T3abN0 rectal adenocarcinoma treated with 3 months of FOLFOX/CAPOX followed by Transanal Endoscopic Surgery (TES). The phase III CO.32/NEO-RT trial (NCT06205485) will compare two organ sparing strategies for patients with stage I rectal cancer. Methods: Eligible patients with clinical stage T1/2 N0 adenocarcinoma with preserved mismatch repair (MMR) will be randomized 1:1 to ARM A, 3 months of FOLFOX or CAPOX versus ARM B, chemoradiation (54 Gy) followed by tumor restaging within 16 weeks of start of therapy. Patients with histological high grade, mucinous or deficient MMR and those that can be treated with tumor excision alone are excluded. The primary endpoint is tumor downstaging to clinical Complete Response (cCR) by pelvic MRI, endoscopy and digital rectal exam. Subsequent TES is recommended for all patients with tumor response and may be done within 24 weeks of treatment begin, followed by 5 years (y) of observation with serial MRI (q6m x 2y then annually) and endoscopy (q4m x 2y, then q6m during year 3, then annually). The co-primary endpoint is Quality Of Life (QOL) measured by the Low Anterior Resection Score (LARS). In a non-inferiority comparison between treatment arms, if the cCR is assumed to be 45% in ARM B and if there is no true difference between ARMS A and B, then 250 patients are required to be 80% sure that the upper limit of a one-sided 90% confidence interval will exclude a difference in favor of chemoradiation of more than 14%. Results: The approved CCTG CO.32 trial is expected to open February, 2024 at Canadian CCTG and US Alliance, ECOG-ACRIN, NRG, and SWOG NCTN sites with an estimated accrual duration of 4 years. Conclusions: The results of this study will have a major impact on the treatment of patients with stage I rectal cancer. Both arms offer the potential of organ preservation and results will inform whether induction chemotherapy is non-inferior to ChemoRT and compare patient QOL and functional outcomes. Clinical trial information: NCT06205485 .

Combined visual and quantitative assessment of somatostatin receptor scintigraphy for staging and restaging of neuroendocrine tumors.

Somatostatin receptor scintigraphy (SRS) using 111In-DTPA-DPhe1-octreotide (pentetreotide) has become an integral part of neuroendocrine neoplasm management. The lack of precise quantification is a disadvantage of SRS. This study aimed to adapt the standardized uptake value (SUV) to SRS, establish the SUV range for physiological uptake in the liver, kidney, and spleen, and elucidate the utility of combined visual and quantitative SRS assessment for staging and restaging of neuroendocrine tumors (NETs). This study included 21 patients with NETs who underwent 111In-pentetreotide SRS. The SUV of physiological and pathological uptake was calculated using bone single-photon emission computed tomography (SPECT) quantitative analysis software (GI-BONE). For visual analysis, the primary and metastatic lesions were scored visually on planar and SPECT images using a five-point scale. We assessed the relationships between the SUVs of the liver, kidney, and spleen in the dual phase, and among quantitative indices, visual score, and pathological lesions classification. Sixty-three NEN lesions were evaluated. The mean ± standard deviation maximum SUVs (SUVmax) were liver: 4h, 2.6 ± 1.0; 24h, 2.2 ± 1.0; kidney: 4h, 8.9 ± 1.8; 24h, 7.0 ± 2.0; and spleen; 4h, 11.3 ± 4.5; 24h, 11.5 ± 7.6. Higher SUVmax was significantly associated with higher visual scores on dual-phase SPECT (4h, p < 0.001; 24h, p < 0.001) (4h: scores 3 and 4, p < 0.05; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01; 24h: scores 3 and 4, p = 0.0748; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01). We adapted the SUV to SRS and established the range of SUV for physiological uptake in the liver, kidney, and spleen. Combined visual and quantitative assessment is useful for imaging individual lesions in greater detail, and may serve as a new tumor marker of SRS for staging and restaging of NETs.

Ultra-High-Resolution T2-Weighted PROPELLER MRI of the Rectum With Deep Learning Reconstruction: Assessment of Image Quality and Diagnostic Performance.

The aim of this study was to evaluate the impact of ultra-high-resolution acquisition and deep learning reconstruction (DLR) on the image quality and diagnostic performance of T2-weighted periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) imaging of the rectum. This prospective study included 34 patients who underwent magnetic resonance imaging (MRI) for initial staging or restaging of rectal tumors. The following 4 types of oblique axial PROPELLER images perpendicular to the tumor were obtained: a standard 3-mm slice thickness with conventional reconstruction (3-CR) and DLR (3-DLR), and 1.2-mm slice thickness with CR (1.2-CR) and DLR (1.2-DLR). Three radiologists independently evaluated the image quality and tumor extent by using a 5-point scoring system. Diagnostic accuracy was evaluated in 22 patients with rectal cancer who underwent surgery after MRI without additional neoadjuvant therapy (median interval between MRI and surgery, 22 days). The signal-to-noise ratio and tissue contrast were measured on the 4 types of PROPELLER imaging. 1.2-DLR imaging showed the best sharpness, overall image quality, and rectal and lesion conspicuity for all readers ( P < 0.01). Of the assigned scores for tumor extent, extramural venous invasion (EMVI) scores showed moderate agreement across the 4 types of PROPELLER sequences in all readers (intraclass correlation coefficient, 0.60-0.71). Compared with 3-CR imaging, the number of cases with MRI-detected extramural tumor spread was significantly higher with 1.2-DLR imaging (19.0 ± 2.9 vs 23.3 ± 0.9, P = 0.03), and the number of cases with MRI-detected EMVI was significantly increased with 1.2-CR, 3-DLR, and 1.2-DLR imaging (8.0 ± 0.0 vs 9.7 ± 0.5, 11.0 ± 2.2, and 12.3 ± 1.7, respectively; P = 0.02). For the diagnosis of histopathologic extramural tumor spread, 3-CR and 1.2-CR had significantly higher specificity than 3-DLR and 1.2-DLR imaging (0.75 and 0.78 vs 0.64 and 0.58, respectively; P = 0.02), and only 1.2-CR had significantly higher accuracy than 3-CR imaging (0.83 vs 0.79, P = 0.01). The accuracy of MRI-detected EMVI with reference to pathological EMVI was significantly lower for 3-CR and 3-DLR compared with 1.2-CR (0.77 and 0.74 vs 0.85, respectively; P < 0.01), and was not significantly different between 1.2-CR and 1.2-DLR (0.85 vs 0.80). Using any pathological venous invasion as the reference standard, the accuracy of MRI-detected EMVI was significantly the highest with 1.2-DLR, followed by 1.2-CR, 3-CR, and 3-DLR (0.71 vs 0.67 vs 0.59 vs 0.56, respectively; P < 0.01). The signal-to-noise ratio was significantly highest with 3-DLR imaging ( P < 0.05). There were no significant differences in tumor-to-muscle contrast between the 4 types of PROPELLER imaging. Ultra-high-resolution PROPELLER T2-weighted imaging of the rectum combined with DLR improved image quality, increased the number of cases with MRI-detected extramural tumor spread and EMVI, but did not improve diagnostic accuracy with respect to pathology in rectal cancer, possibly because of false-positive MRI findings or false-negative pathologic findings.

Diagnostic performance of endorectal ultrasound combined with shear wave elastography for rectal tumors staging.

This study aims to analyze the performance of endorectal ultrasound (ERUS) combined with shear wave elastography (SWE) for rectal tumor staging. Forty patients with rectal tumors who had surgery were enrolled. They underwent ERUS and SWE examinations before surgery. Pathological results were used as the gold standard for tumor staging. The stiffness values of the rectal tumor, peritumoral fat, distal normal intestinal wall, and distal perirectal fat were analyzed. The diagnostic accuracy of ERUS stage, tumor SWE stage, ERUS combined with tumor SWE stage, and ERUS combined with peritumoral fat SWE stage were compared and evaluated by receiver operating characteristic (ROC) curve to select the best staging index. From T1 to T3 stage, the maximum elasticity (Emax) of the rectal tumor increased gradually (p < 0.05). The cut-off values of adenoma/T1 and T2, T2 and T3 tumors were 36.75 and 85.15kPa, respectively. The diagnostic coincidence rate of tumor SWE stage was higher than that of ERUS stage. Overall diagnostic accuracy of ERUS combined with peritumoral fat SWE Emax restaging was significantly higher than that of ERUS. ERUS combined with peritumoral fat SWE Emax for tumor restaging can effectively distinguish between stage T2 and T3 rectal tumors, which provides an effective imaging basis for clinical decisions.

18F] AlF‑NOTA‑FAPI‑04 PET/CT as a promising tool for imaging fibroblast activation protein in gastrointestinal system cancers: a prospective investigation of comparative analysis with 18F-FDG

PurposeThe radiopharmaceutical [18F]AlF-NOTA-FAPI-04 presents a promising alternative to 68 Ga-FAPI owing to its relatively longer half-life. This study aimed to evaluate the clinical usefulness of [18F]AlF-NOTA-FAPI-04 PET/CT for the diagnosis of primary and metastatic lesions in various types of gastrointestinal system cancers, compared with 18F-FDG PET/CT.MethodsPatients diagnosed with gastrointestinal system malignancies were prospectively enrolled. All patients underwent both 18F-FDG and 18F-FAPI-04 PET/CT scans within one week, with 44 (73.3%) for cancer staging and 16 (26.7%) for tumor restaging. Diagnostic efficacy of the primary tumor, as well as the presence and number of lymph nodes and distant metastases, were assessed. Tumor uptake was quantified by the maximum standard uptake value (SUVmax).ResultsFor detection of primary tumor, the diagnostic sensitivity of 18F-FDG PET/CT was 72.7%, while it was 97.7% for 18F-FAPI-04 PET/CT. Based on per-lymph node analysis, the sensitivity, specificity, and accuracy of 18F-FAPI-04 PET/CT in diagnosing metastatic lymph nodes were 91.89%, 92.00%, and 91.96%, respectively. These values were notably higher than those 18F-FDG PET/CT (79.72%, 81.33% and 80.80%, respectively). The 18F-FAPI-04 PET/CT surpassed 18F-FDG PET/CT in detecting suspected metastases in the brain (7 vs. 3), liver (39 vs. 20), bone (79 vs. 51), lung (11 vs. 4), and peritoneal carcinoma (48 vs. 22). Based on per-patient analysis, differential diagnostic accuracies (18F-FAPI-04 vs. 18F-FDG PET/CT) were observed in all patients (91.7% vs. 76.7%), the initial staging group (90.9% vs. 79.5%), and the re-staging group (93.8% vs. 68.7%). Additionally, 18F-FAPI-04 PET/CT revised final diagnosis in 31.7% of patients, contrasting with 18F-FDG PET/CT, and prompted changes in clinical management for 21.7% of the patients.Conclusion18F-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in delineating the primary gastrointestinal tumors and detecting suspected metastatic lesions due to a higher target-to-background ratio (TBR). Moreover, 18F-FAPI-04 PET/CT could provide valuable guidance for tumor staging, thereby having a potential impact on patient management.

Restaging rectal cancer following neoadjuvant chemoradiotherapy.

Correct tumour restaging is pivotal for identifying the most personalised surgical treatment for patients with locally advanced rectal cancer undergoing neoadjuvant therapy, and works to avoid both poor oncological outcome and overtreatment. Digital rectal examination, endoscopy, and pelvic magnetic resonance imaging are the recommended modalities for local tumour restaging, while chest and abdominal computed tomography are utilised for the assessment of distant disease. The optimal length of time between neoadjuvant treatment and restaging, in terms of both oncological safety and clinical effectiveness of treatment, remains unclear, especially for patients receiving prolonged total neoadjuvant therapy. The timely identification of patients who are radioresistant and at risk of disease progression remains challenging.

Advanced iron oxide nanotheranostics for multimodal and precision treatment of pancreatic ductal adenocarcinoma.

Despite current advances in new approaches for cancer detection and treatment, pancreatic cancer remains one of the most lethal cancer types. Difficult to detect early, aggressive tumor biology, and resistance to chemotherapy, radiotherapy, and immunotherapy result in a poor prognosis of pancreatic cancer patients with a 5-year survival of 10%. With advances in cancer nanotechnology, new imaging and drug delivery approaches that allow the development of multifunctional nanotheranostic agents offer opportunities for improving pancreatic cancer treatment using precision oncology. In this review, we will introduce potential applications of innovative theranostic strategies to address major challenges in the treatment of pancreatic cancer at different disease stages. Several important issues concerning targeted delivery of theranostic nanoparticles and tumor stromal barriers are discussed. We then focus on the development of a magnetic iron oxide nanoparticle platform for multimodal therapy of pancreatic cancer, including MRI monitoring targeted nanoparticle/drug delivery, therapeutic response, and tumor re-staging, activation of tumor immune response by immunoactivating nanoparticle and magnetic hyperthermia therapy, and intraoperative interventions for improving the outcome of targeted therapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Integration of molecular imaging in the personalized approach to neuroendocrine tumors.

NETs lesions can be difficult to characterize with conventional anatomic imaging (CT and MRI). Functional imaging techniques, and especially PET imaging, are very useful for detecting small neuroendocrine tumors that would not be seen with other techniques. The role of nuclear medicine in the localization, staging, restaging, treatment and monitoring of neuroendocrine tumors (NETs) has become progressively more relevant due to: the availability of tracers on new targets, tracers for positron emission tomography (PET); the development of cyclotrons and generators that allow this availability; as well as to hybrid systems (SPECT/CT, PET/CT and PET/MRI) that, by joining the functional and anatomical image, improve the quality of the images. Teragnosis, a new emerging therapy, in NET used receptor-mediated or nonreceptor- mediated mechanism to facilitate penetration and high-affinity binding between the radiopharmaceutical and the tumor cell. Teragnosis offers the possibility of personalized targeted radionuclide therapy.

Short Latency Radiation Induced Osteosarcoma Detected on 18F-FDG PET/CT Scan in Solitary Plasmacytoma.

18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays a pivotal role in the staging, restaging, and surveillance of various bone tumors, including plasmacytomas and osteosarcomas. Solitary plasmacytomas most frequently occur in the bones and are primarily treated with either surgery or radiotherapy. Radiation-induced osteosarcomas (RIOS) usually develop after a median interval of 11 years between radiation and sarcoma presentation. However, these can rarely present with a short latent period of 4 years or even lesser. In such cases, whole-body imaging plays a vital role in the early detection and management of RIOS. Herein, we present the case of a 29-year-old female patient with solitary plasmacytoma undergoing a follow-up whole-body 18F-FDG PET/CT, which revealed metastatic RIOS after a short latent period.

68Ga-DOTATATE PET/CT versus 111In-octreotide scintigraphy in patients with neuroendocrine tumors: a prospective study.

ObjectiveTo compare 68Ga-DOTA-DPhe1,Tyr3-octreotate (68Ga-DOTATATE) positron-emission tomography/computed tomography (PET/CT) findings with those of conventional 111In-octreotide scintigraphy in patients with neuroendocrine tumors (NETs).Materials and MethodsThis was a single-center prospective study including 41 patients (25 males; mean age, 55.4 years) with biopsy-proven NETs who underwent whole-body 111In-octreotide scintigraphy and whole-body 68Ga-DOTATATE PET/CT. The patients had been referred for tumor staging (34.1%), tumor restaging (61.0%), or response evaluation (4.9%). Images were compared in a patient-by-patient analysis to identify additional lesions, and we attempted to determine the impact that discordant findings had on treatment planning.ResultsCompared with 111In-octreotide scintigraphy, 68Ga-DOTATATE PET/CT revealed more lesions, the additional lesions typically being in the liver or bowel. Changes in management owing to the additional information provided by 68Ga-DOTATATE PET/CT occurred in five patients (12.2%), including intermodal changes in three (7.3%) and intramodal changes in two (4.9%). In addition, 68Ga-DOTATATE PET/CT yielded incidental findings unrelated to the primary NET in three patients (7.3%): Hürthle cell carcinoma of the thyroid, bowel non-Hodgkin lymphoma, and a suspicious breast lesion.ConclusionWe conclude that 68Ga-DOTATATE PET/CT is superior to conventional 111In-octreotide scintigraphy for the management of NETs because of its ability to determine the extent of the disease more accurately, which, in some cases, translates to changes in the treatment plan.

Whole-body hybrid positron emission tomography imaging yields clinically relevant information in the staging and restaging of sinonasal tumors.

BackgroundWhole‐body hybrid positron emission tomography (PET) imaging is increasingly used for sinonasal tumors. However, only empirical data exist on the additional, clinically relevant information derived from these techniques.MethodsThis study included 96 regionalized magnetic resonance imaging (MRI) of the sinonasal tract/neck and separate hybrid FDG‐PET/CT or FDG‐PET/MRI in 74 patients. Additional radiological information (ARI) obtained from each hybrid examination was analyzed and its clinically relevance was determined. Clinically relevant information (CRI) was categorized with regard to primary tumor site, regional lymph node metastases, distant metastases, second primary tumors, and non‐neoplastic findings.ResultsA total of 45/96 (46.9%) hybrid PET examinations revealed ARI. CRI was found in 32/96 (33.3%) examinations and concerned the primary tumor site (6.1%), regional lymph node metastases (4.1%), distant metastases (14.3%), second primary tumors (7.3%), and non‐neoplastic findings (5.1%).ConclusionsHybrid PET imaging yields additional radiological information translating into clinically relevant information in a substantial proportion of patients with sinonasal tumors.

Recent advances in convex probe endobronchial ultrasound: a narrative review.

Convex probe endobronchial ultrasound (CP-EBUS) has been widely used in the lymph node staging and restaging of lung tumors and the diagnosis of mediastinal diseases. Recent years have seen continuous progress in this technology. For diagnosis, elastography technology can preliminarily distinguish between benign and malignant lesions, so that reduce the number of punctures. CP-EBUS can also be used as an endoscopic ultrasound (EUS) to guide needle aspirations of liver lesions, retroperitoneal lymph nodes and left adrenal gland (LAG) lesions sometimes. Some advances help diagnosing more accurately and effectively, such as the intranodal forceps biopsy (IFB), the new type of 22G needle, the rapid on-site evaluation (ROSE) and the cancer gene methylation, etc. In addition, special advances are being made in diagnosis using artificial intelligence (AI). For treatment, CP-EBUS has yielded novel research results when applied to transbronchial needle injection (TBNI) and radioactive seed implantation in clinical cases, and blocking of the cardiac plexus in animal studies. The next-generation CP-EBUS is also ready for use in the clinic and the technology will be improving continuously. Through this review, we hope to educate clinicians on the latest uses of CP-EBUS and open up further research ideas for readers interested in this technology.

Increasing prevalence of HPV in oropharyngeal carcinoma suggests adaptation of p16 screening in Southeast Asia.

Human papillomavirus (HPV) is etiologically linked to increasing oropharyngeal squamous cell carcinoma (OPSCC) rates in the Western world. However, the role of HPV in Southeast Asia, a high incidence region, hasn't been assessed. 96 formalin-fixed, paraffin-embedded (FFPE) tissue blocks and corresponding patient data were obtained from Srinagarind Hospital, Thailand from 2012-2017. DNA from areas of 70 %+ cellularity were genotyped using polymerase chain reaction (PCR) and stained for p16, a surrogate marker for HPV. Inverse probability weights based on data from the hospital-based cancer registry were used in statistical analyses. Adjusted linear regression was used to assess changes in OPSCC HPV prevalence and conduct projections. Kaplan-Meier and Cox proportional hazard models were used to determine HPV-specific survival differences. 14 patients exhibited monoinfection with HPV16, two with HPV18 and one was HPV16/18 coinfected. PCR results were in agreement with p16 staining. On average, HPV + patients were more likely to have tonsil cancer (p-value:0.002). HPV prevalence increased by 2% annually (pvalue: 0.01), from 16 % in 2012 to 26 % in 2017. At the current rate, OPSCC HPV positivity will exceed 50 % by 2030. HPV positivity was shown to be protective in Kaplan-Meier (log-rank p = 0.02) and sex, age and stage adjusted Cox models (HR:0.34 [95 %CI:0.22, 0.52]). Given the increased prevalence and similarities in presentation of HPV + OPSCC to those observed in Western countries, the data suggest the adaptation of p16 staining and subsequent restaging of OPSCC tumors as suggested by the American Joint Committee on Cancer in Southeast Asia.

Phantom simulation of liver metastasis on a positron emission tomography with computed tomography scan after neoadjuvant chemoradiotherapy for distal esophageal cancer: a case report

BackgroundNeoadjuvant chemoradiotherapy is currently the gold standard treatment for esophageal cancer prior to surgery. This radiation therapy will sometimes lead to liver damage parallel to esophageal lesions, which mimics liver metastasis visualized by 18F-fluorodeoxyglucose positron emission tomography with computed tomography. In this report, we publish virtual radiation-induced liver damage images obtained during surgery, along with the coherent pathology, in order to confirm the false-positive result through an optimally decisive radiological examination.Case presentationWe report a case of a Asian male patient with distal esophageal cancer who had undergone neoadjuvant chemoradiotherapy (5000 cGy). Subsequently, a new lesion was discovered during a positron emission tomography with computed tomography scan 6 weeks later, near the left caudate lobe of the liver during tumor restaging. To exclude the possibility of liver metastasis, serial imaging was conducted, which included liver sonography, computed tomography, and magnetic resonance imaging for a more intimate probe. The patient’s condition was verified as being liver inflammation change, as seen by the liver magnetic resonance imaging presentation. Thoracoscopic esophagectomy was performed with cervical esophagogastrostomy via the retrosternal route, along with a feeding jejunostomy. The procedure was performed smoothly, with an intraoperative liver biopsy also being conducted 2 weeks later, after positron emission tomography with computed tomography restaging. The pathology report revealed esophageal cancer in the form of poorly differentiated squamous cell carcinoma, pT3N1M0. The liver biopsy revealed obvious inflammation change after radiation therapy, which elucidated sinusoidal congestion with the attenuated hepatic cords and filled with erythrocytes. There was no evidence of liver metastasis. The patient recovered uneventfully and was discharged with his oral intake performing smoothly, and a stable condition was observed during 12 months of outpatient department follow-up.ConclusionsNew foci of increased 18F-fluorodeoxyglucose avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation for distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease. Awareness of the pitfalls of a high 18F-fluorodeoxyglucose uptake in radiation-induced liver injury is crucial in order to avoid misinterpretation and overstaging. Except for the location of 18F-fluorodeoxyglucose uptake, the shape of the lesion, and an maximum standardized uptake value (> 10/h), a convincing liver magnetic resonance imaging scan or even a liver biopsy can provide accurate information for distinguishing radiotherapy-induced liver injury from liver metastasis.

Breast cancer grade and clinical benefit in patients with advanced breast cancer treated with an engineered whole tumor cell-targeted immunotherapy alone or in combination with checkpoint inhibition.

3033 Background: SV-BR-1 is a breast cancer cell line derived from a grade II (moderately differentiated) tumor. SV-BR-1 was transfected with the CSF2 gene (encoding GM-CSF) to form SV-BR-1-GM. SV-BR-1-GM expresses HLA class I &amp; II antigens and has functional antigen-presenting cell activity, directly stimulating CD4+ T cells in an HLA-DR restricted fashion. The SV-BR-1-GM regimen consists of low-dose cyclophosphamide (300 mg/m2) to reduce immune suppression, intradermal inoculation with irradiated SV-BR-1-GM (20x106 cells divided into 4 sites) and interferon-α2b (10,000 IU into each inoculation site ~2 &amp; 4 days later) to boost the response. Here, we evaluate the impact of tumor grade on clinical benefit following treatment with the SV-BR-1-GM regimen. Methods: Patients with advanced breast cancer were treated with either the SV-BR-1-GM regimen alone or with the SV-BR-1-GM regimen with pembrolizumab. For the SV-BR-1-GM regimen alone, cycles were administered every 2 weeks x 3 and then monthly, while combination with pembrolizumab (200 mg IV 1-5 days following SV-BR-1-GM inoculation) administered cycles every 3 weeks. Tumor restaging was every 6-12 weeks. Results: 33 patients were enrolled. The treatment was generally safe with inoculation site pruritis, erythema and induration the most common adverse events. 23 patients had grade III (poorly differentiated) tumors, 9 had grade II tumors and one had a grade I (well differentiated) tumor. None of the patients with grade III tumors exhibited clinical benefit. 7 patients with grade I/II tumors received the SV-BR-1-GM regimen alone, 2 received the SV-BR-1-GM regimen with pembrolizumab and 1 received both regimens. As noted in the Table, 7 patients experienced clinical benefit including all 3 patients treated in combination with pembrolizumab. This included 6 patients with stable disease and one with a partial response. Conclusions: The SV-BR-1-GM regimen with or without pembrolizumab appears safe and able to induce clinical benefit even in very heavily pre-treated patients with low or intermediate grade advanced breast cancer. Clinical trial information: NCT03328026 . [Table: see text]

Technology-enabled longitudinal monitoring of patient-reported outcomes (PROs) to individualize care of immune-related adverse events (irAEs) in patients (pts) treated with immune checkpoint inhibitors (ICIs).

TPS2088 Background: ICIs have become the therapeutic standard for many cancers but are associated with unique and diverse irAEs that often occur at home. Appropriately timed and specific interventions are critical to recovery. Thus, there is a need to effectively &amp; efficiently monitor in real time pts treated with ICIs. To improve outcomes, we have activated a clinical trial developed to determine the feasibility and safety of an electronically enabled strategy to remotely monitor symptoms and prompt communication that will guide and inform specific patient-driven “course corrections” in response to potential irAEs. Methods: This is an adaptive prospective trial that uses a mobile irAE-specific PRO application we developed to monitor and alert the care team in real time when severe symptoms are reported. In parallel with the mobile symptom collection, serum and urine biomarkers are collected at baseline, first tumor restaging, and upon the development of irAEs. Optional stool microbiome analyses are also performed. To facilitate the generalizability of our inferences, we are using broad inclusion criteria: ECOG performance status ≤3; any line of ICI given as standard of care or as part of therapeutic clinical trials; elderly pts are included. Because the relationship between PROs and irAEs is currently undefined, we designed our trial to use adaptive symptom thresholds that will notify the healthcare team of suspicion for irAEs. The mobile application will use these dynamic thresholds to determine whether or not to alert the healthcare team. The positive and negative predictive value of each symptom for identifying subsequent irAEs will be assessed at scheduled interim analysis time points. The care teams’ responses to the alerts, and all of the clinical outcomes for the pts over time will be collected as part of the trial. The primary goal of the trial is the assessment of the predictive power of the mobile PRO symptom collection in combination with serum and urine markers to identify grade 2 or higher adverse events that require intervention (e.g., dose modifications, hospitalizations, and therapeutic interventions) within two weeks of symptom onset. Effective remote monitoring of irAEs will leverage our understanding of ICI toxicity and empower pts to be effective partners in their care. The trial has currently enrolled 17 pts towards the enrollment target of 100 pts. Clinical trial information: PA19-0095 .

Radiolabeled somatostatin analogues for the diagnosis and therapy of NETs: upcoming new strategies

Octreotide is the progenitor of the somatostatin analogues (SSA) family, which includes radiopharmaceuticals suitable for SPECT, PET and radionuclide therapy, within an effective theragnostic model. Nowadays, PET/CT performed using DOTA peptides radiolabeled with Gallium-68 is considered the best molecular imaging procedure in staging and restaging of neuroendocrine tumors (NETs), while new SSA are being successfully developed for Peptide Receptor Radionuclide Therapy (PRRT). Technological developments both in the area of PET and MRI are likely to open new avenues for the optimization of the diagnostic workup of NETs. The aim of this paper is to present an up-to-date overview of the role of diagnostic 68Ga-SSA/PET hybrid imaging with MRI or CT, for the workup of NETs, as well as the perspectives arising from the use of therapeutic SSA radiopharmaceuticals either alone or in combination with cold SSA. A literature review of the most relevant papers in the field of radiolabeled SSA used for diagnosis or therapy demonstrates that PET/MRI as compared to PET/CT has a slightly higher diagnostic accuracy in detecting liver metastases but a lower accuracy in detecting pulmonary secondary lesions. In the present scenario, PET/CT remains the most cost-effective choice, integrated with an abdominal MRI when needed. Concurrently with the growth of PRRT performed with Lutetium-177 or Yttrium-90 DOTA peptides, new strategies to improve the therapeutic outcome are being sought with combined treatments using radioactively labeled SSA along with cold SSA. Interesting perspectives are opened by the availability of PET/MRI and full digital PET/CT due to the improved detector sensitivity and spatial resolution. At the same time, new strategies will be sought based on the association of PRRT with old and/or newer oncologic therapeutic strategies, or on the use of radionuclide cocktails. An intriguing future can be envisaged due to the commercial availability of radiopharmaceuticals labeled with alpha emitting radionuclides, which may allow better results compared to beta-emitters, likely due to the bystander and/or abscopal effect.

Comparison between laparoscopy and laparotomy in the surgical re-staging of granulosa cell tumors of the ovary

ObjectiveTo evaluate the role of laparoscopic (LPS) and laparotomic (LPT) re-staging in patients with incompletely surgically staged ovarian granulosa cell tumors (OGCT). MethodsWe conducted a medical chart retrospective analysis of all patients with sex cord stromal tumors (SCSTs) who were managed in our division between March 1994 and March 2017. After a complete review of surgical and pathological notes, patients with incomplete staging were restaged according to the FIGO guidelines. Statistical analysis was conducted using Statistical Package version 20.0 for Windows (SPSS, Inc., Chicago, Illinois). ResultsOut of a total of 170 patients SCSTs, 84 patients (49,5%) received primary surgery that included a hysterectomy; 86 patients (50,5%) underwent fertility-sparing surgery. Eighty-one patients (48%) with diagnosis of OGCT were incompletely surgically staged at another institution. We evaluated our results in terms of laparoscopic approach (56 patients) and open treatment (25 patients). Among the IA patient's group, 1 was upstaged to IIB stage and 2 to IIIB; among patients with IC stage, 1 was upstaged to IIA, 2 to IIB and 1 to IIIB stage. Adjuvant chemotherapy was given to the upstaged patients with final stage IIB-IIIC. No statistically significant difference between laparoscopy and open-surgery was detected in terms of upstaged patients after second surgery (p = 0,36). ConclusionAccording to our series, laparoscopic restaging compared to the open approach seems to be a feasible and efficient technique to complete surgical staging in patients with GCTs incorrectly staged. Surgical restaging seems to upstage a considerable number of OGCT, mainly in the initial stage IC group of patients. However, the impact of restaging on final outcome and survival remains to be demonstrated.

Abstract B001: Safety and efficacy of ZW25, a HER2-targeted bispecific antibody, in combination with chemotherapy in patients with locally advanced and/or metastatic HER2-expressing gastroesophageal cancer

Abstract Background: Up to 30% of gastroesophageal adenocarcinoma (GEA) overexpress HER2. ZW25 is a novel bispecific antibody that targets HER2 domains ECD2 and ECD4, resulting in multiple differentiated and unique mechanisms of action, including increased antibody binding density and improved receptor internalization and downregulation relative to trastuzumab. In an ongoing phase 1 trial (ZWI-ZW25-101; NCT02892123), single-agent ZW25 was well tolerated and showed promising anti-tumor activity across HER2-expressing solid tumors. This abstract presents data for GEA patients treated with ZW25 in combination with chemotherapy in Study ZWI-ZW25-101. Methods Eligible patients had HER2-expressing (IHC 3+, IHC 2+/FISH+, or IHC 2+/FISH-) GEA and had disease progression after 1–3 lines of prior chemotherapy for advanced and/or metastatic disease. Fresh or archived tumor tissue was required for central review of HER2 status, although patients could be enrolled based on local results. Patients received ZW25 in combination with paclitaxel or capecitabine. Evaluations included standard safety assessments, tumor re-staging (Q8W by RECIST 1.1), and assessment of peak/trough pharmacokinetic (PK) levels during each cycle. Results To date, 14 patients have been enrolled, with safety and efficacy data available for 11. ZW25 was administered in combination with paclitaxel (n=5) or capecitabine (n=6). The median age was 62 yrs (range, 26-80). The median number of prior anti-cancer regimens was 3 and the median number of prior HER2-targeted therapies was 1. Six patients (55%) were HER2 IHC3+ or IHC2+ and FISH+ per central review. The most common adverse events (AEs) considered related to ZW25 or ZW25 and chemotherapy were diarrhea (n=5; 45%), fatigue (n=3; 27%), and nausea (n=3; 27%); the majority of events were Grade 1 or 2. Grade 3 or higher events considered related to ZW25 or ZW25 and chemotherapy occurred in 3 patients (27%), including fatigue, hypokalemia, and neutropenia (n=1 each). One additional patient experienced a Grade 5 serious adverse event of pneumonitis, reported as related to the combination of ZW25 and paclitaxel. This patient had been previously treated with trastuzumab, cisplatin, and capecitabine; pembrolizumab and margetuximab; and most recently DS8201, and had asymptomatic interstitial lung disease at study entry. A total of 9/11 patients (82%) had measurable disease and 8/9 (89%) were response-evaluable. The objective response rate was 63% (95% CI: 25, 92) (5/8 patients; all partial responses, with 4 confirmed to date) and the disease control rate was 75% (6/8 patients). Responses were seen in patients with FISH+ and FISH- disease, as well as in combination with either paclitaxel or capecitabine. Patients have received between 1 and 12 cycles of treatment and 4 patients remain on treatment. PK data will be presented at the meeting. Conclusions The combination of ZW25 with chemotherapy was generally well tolerated in heavily pre-treated patients with HER2 high- and low-expressing GEA and the preliminary anti-tumor activity is promising. Further evaluation of the safety and efficacy of ZW25 in combination with standard of care chemotherapy regimens has been initiated in frontline GEA (ZW25-201; NCT03929666). Citation Format: Funda Meric-Bernstam, Jorge Chaves, Do-Youn Oh, Jeeyun Lee, Yoon-Koo Kang, Erika Hamilton, Jose Mayordomo, Melody Cobleigh, Christos Vaklavas, Elena Elimova, Jaffer Ajani, Jordi Rodon, Gerry Rowse, Todd Gray, Rose Lai, Diana Hanna. Safety and efficacy of ZW25, a HER2-targeted bispecific antibody, in combination with chemotherapy in patients with locally advanced and/or metastatic HER2-expressing gastroesophageal cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B001. doi:10.1158/1535-7163.TARG-19-B001

Agreement Between the European Organization for Research and Treatment of Cancer and Positron Emission Tomography Response Criteria in Solid Tumors in Evaluating Treatment Response in Solid Malignant Tumors.

IntroductionFluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is used for non-invasive staging and restaging of solid malignant tumors. PET-CT based criteria have been developed to evaluate the response to targeted therapy. These include the European Organization for Research and Treatment of Cancer (EORTC) and the PET Response Criteria in Solid Tumors (PERCIST). The aim of this study was to determine the agreement between EORTC and PERCIST criteria for treatment response evaluation in patients with solid malignant tumors.Materials and methodsThis was a retrospective study conducted from February 2017 till July 2017. Electronic medical records of patients diagnosed with solid malignant tumors were searched. Experienced radiologists evaluated the PET-CT images based on EORTC and PERCIST criteria. The Kappa (κ) test was used for evaluation of agreement between treatment response according to EORTC and PERCIST criteria.ResultsOut of 54 patients, 41 (75.9%) were male and 13 (24.1%) were female with a mean age of 57.09 ± 10.65 years. According to EORTC criteria, complete metabolic response (CMR) was seen in five (9.3%) of patients, partial metabolic response (PMR) was seen in 36 (66.7%) of patients, progressive metabolic disease (PMD) was seen in nine (16.7%) of patients and stable metabolic disease (SMD) was seen in four (7.4%) of patients. According to PERCIST criteria, CMR was seen in five (9.3%) of patients, PMR was seen in 33 (61.1%) of patients, PMD was seen in nine (16.7%) of patients and SMD was seen in seven (13.0%) of patients. EORTC and PERCIST agreed on 43 (79.6%) of the patients with κ-coefficient of 0.62 indicating good agreement (p-value of <0.001).ConclusionEORTC and PERCIST criteria have a good agreement in evaluating treatment response in solid malignant tumors. Therefore, adoption of EORTC or PERCIST in PET-CT reporting can standardize the evaluation of oncological treatment results.