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Introduction: Adjuvant anti-cancer systemic therapy (SACT) following lung resection improves overall survival in stage II/II non-small cell lung cancer (NSCLC). The Getting It Right First Time (GIRFT) National Specialty Report for Lung Cancer recommends centres publish adjuvant SACT rates for National benchmarking and proposes a target of >40% of eligible patients undergo SACT. We report a regional audit into the uptake of adjuvant SACT in Greater Manchester (GM). Method(s): A retrospective case review of all patients undergoing curative-intent NSCLC surgery with a pathological stage of II/III from 01/01/21 to 30/04/21. Data collected included patient demographics, uptake of adjuvant SACT, reasons for no adjuvant SACT and tolerance and complications of SACT. Result(s): 58 patients underwent surgical resection within the audit period and were eligible for adjuvant SACT. Median age was 70 years (range 45 - 81) and 60% were female. 47% (27/58) commenced adjuvant SACT;41% (24/58) were treated with chemotherapy and 7% (4/58) were treated with tyrosine kinase inhibitors. 58% (14/24) of patients that commenced adjuvant chemotherapy completed 4 cycles. Carboplatin/Vinorelbine was the commonest regimen (82%, 18/22). There were no grade III-V complications and no chemotherapy-related deaths. Dose reduction due to toxicity was required in 14% (3/22). The reasons adjuvant systemic therapy was not given were patient choice in 32% (10/31), poor physical health such that risks outweighed benefits in 42% (13/31), and other reasons (e.g. need to treat synchronous primary tumours) in 26% (8/31). COVID-19 was not recorded as a cause for adjuvant omission/ dose reduction. Conclusion(s): This data provides national benchmarking information for adjuvant SACT in NSCLC and suggests the target of >40% is achievable and appropriate. Interventions that improve patient fitness pre- and post-operatively might increase adjuvant SACT uptake. This regional audit will be extended to review all eligible patients in 2021 and further data will be presented. Disclosure: No significant relationships.Copyright © 2023 Elsevier B.V.
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Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.
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Introduction: Hepatocellular carcinoma (HCC) comprises the majority of primary liver cancer and has a poor prognosis. Clivus metastasis is rare with only a few reported cases in the medical literature. We report a case of a patient who presented with clival mass found to have metastatic HCC. Case Description/Methods: A 63-year-old woman presented for neurosurgical evaluation after she was found to have a skull base mass on computerized tomography (CT) of the head at an outside hospital. She endorsed dysphagia for three months, however denied headaches or visual disturbances. A magnetic resonance imaging (MRI) revealed a 5.4 cm by 2.9 cm by 3.6 cm mass in the clivus, which was deemed as the cause of dysphagia (Figure 1a). The patient subsequently underwent an endoscopic transsphenoidal resection of the clival mass. Histopathology from the tissue revealed a hepatoid carcinoma, concerning for metastatic HCC (Figure 1b and 2c). Immunohistochemical strains were positive for hepatocytic marker arginase-1 (Figure 1d). Laboratory studies revealed alpha fetoprotein (AFP) of 56,344 ng/mL, CA-125 of 376 ng/mL, normal B-HCG and carcinoembryonic antigen (CEA). Thereafter, a triple phase CT of the liver revealed two LI-RADS 5 lesions suggestive of HCC as the primary malignancy. Patient's case was discussed at multidisciplinary tumor board with recommendations for systemic immunotherapy with atezolimumab plus bevacizumab and radiation therapy to the clivus. Discussion(s): The incidence of HCC has almost tripled since the 1980s making it the fastest rising cause of cancer related deaths. Metastasis to the brain comprises 0.26% to 2.2% of cases and the skull base is the most rarely affected anatomical site. Although CNS presentation is rare, we may see more neurological manifestations of metastatic HCC with the persistence of chronic hepatitis infections, the rise of metabolic diseases such as NASH, and an increase in alcohol-related liver disease during the COVID-19 pandemic. Although exceedingly rare, metastasis to the clivus should be considered in the differential diagnosis of skull base masses. Despite detection and treatment, prognosis remains poor and emphasis should be placed on consistent HCC surveillance. This case emphasizes that skull masses must be evaluated diligently as they can be the first sign of underlying liver malignancy. Given the morbidity and mortality associated with HCC, recognition of atypical manifestations of HCC can lead to a prompt diagnosis and initiation of life-saving treatment. (Figure Presented).
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Objective: Although these days the priority is to fight the Covid-19 pandemic, the importance of human papillomavirus (HPV) infection is not to be neglected. Mechanism: Cervical cancer is caused mainly by a chronic infection with one or more of the high-risk subtypes of HPV -most commonly a sexually transmitted disease acquired early in life. Most HPV infections go away on their own, but some can lead to a precancerous state that, if left untreated, can undergo complete neoplastic transformation. Findings in Brief: There is a hope that in the future the combination of screening tests with vaccinations against oncogenic strains of HPV will allow reductions in the percentage of those contracting cervical cancer. Conclusion(s): The importance of educational activities should be emphasized in developmental gynecology in the context of oncological prevention. The roles of both doctors and nurses are important here. During the Covid-19 Pandemic, these kinds of activities are not to be abandoned. In addition, efforts should be made to develop more practical and workable HPV and cervical screening strategies for use during a pandemic.Copyright © 2022 The Author(s). Published by IMR Press.
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Background Development of immunotherapy/molecular targeted therapy has significantly increased survival/QoL in advanced stages of NSCLC. Aim(s): to analyze outcome predictors, surrogate outcomes, and PROMs after neoadjuvant immunotherapy for initially unresectable NSCLC. Methods Initially unresectable NSCLC (2014-2021) patients who received immunotherapy +/- platinum-based chemo and/or radiotherapy evaluated after response (reduction of primary tumor and/or mediastinal lymphadenopathy/control of distant metastatic disease underwent surgical resection). PROMs were recorded using EORTC QLQ-29. Results 19 underwent salvage surgery after ICI. 14 had partial response (73.6%), 5 stable disease. Diagnosis was achieved by endobronchial ultrasound (EBUS) in 8 (42.1%), fine-needle aspiration biopsy (FNAB) in 7 (36.8%), metastasis biopsy in 4 (21.0%). 11 (57.9%) were treated with neoadjuvant platinum-based chemo before or with ICI, 1 (5.2%) pemetrexed before ICI, 5 (26.3%) radiotherapy for metastatic control. 3 (15.7%) had ICI adverse effects. Radiotherapy was never used preoperatively for pulmonary/mediastinal disease. 7 (36.8%) received adjuvant therapy (5 [26.3%] pembrolizumab, 1 [5.2%] pemetrexed, 1 [5.2%] pemetrexed + pembrolizumab). 4 (21.0%) had local relapse (no systemic relapse). Median OS was 19 months (range: 2-57.4). At 2 months, 94.7% were alive (6 months: 89.5%;31 months: 79.5%). 2 (10.5%) had local recurrence. 2 (10.5%) died due to recurrence, 1 (5.2%) to COVID. 4 (21.0%) relapsed (median DFS: 5.3 months [range: 2.2-13.0]). PROMs were reviewed retrospectively at 30 days/1 year with significant decrease in coughing, side effects of treatment, surgery-related problems. [Formula presented] Conclusions Radical surgical resections following definitive immunotherapy/immune-chemotherapy in selected initially unresectable NSCLC are feasible and safe (low surgical-related mortality and morbidity). Symptoms and surgery-related outcomes were lower with higher QoL due to a selected group of highly motivated patients. Legal entity responsible for the study The authors. Funding Ministero della Salute. Disclosure All authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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Background: Neoplastic pericardial effusion (NPE) is a serious complication that occurs in the setting of advanced oncological disease and is associated with a high recurrence rate. Currently, pericardiocentesis (PCT) remains the first therapeutic option and the use of percutaneous balloon pericardiotomy (PBP) is limited to the treatment of recurrences. However, it is not known whether some aspects of the procedure during PBP lead to different outcomes in terms of survival and recurrence, and no such patients have been included in studies during COVID-19 pandemic. Purpose(s): The aim is to analyses the success, complications and recurrence rate (defined as recurrence of NPE requiring PCT, PBP or surgical pericardial window (SPW) of both procedures (BP) in order to establish the optimal entry treatment for these patients. Method(s): This research analyzed the clinical characteristics and prognostic factors of patients with severe pericardial effusion of neoplastic etiology who underwent PBP during the COVID-19 pandemic. A prospective study was conducted involving 23 patients admitted between January 2020 and January 2022 for severe NPE who underwent PCT or PBP as initial treatment of NPE. Result(s): We included 23 patients, 62.9% were male with a mean age of 51.2+/-14.9 years NPE was the first manifestation of the oncological process in 12 patients (52.1%) with lung cancer being the most frequently associated primary cancer (58.7%) followed by breast cancer in 12.7% of cases. A total of 26 procedures were performed, 10 PCT, 15 PBP, 1 SPW, with tumors cells identified in the pericardial fluid in 13.0% of cases. PCT was used as an entry point in 10 patients (43.5%), 6 patients were COVID-19 positive and PCT was performed as the first treatment. While PBP was chosen as the first therapeutic option in 13 patients (56.5%) (2 Re-PBP). The initial efficacy of the procedure was 93.1% and 92.2% respectively (p=0.88), with 1 complication occurring in the PBP group but not requiring scheduled SPW. In the former group, the percentage of recurrences was higher (34.7%;8 recurrences in 10 patients) compared to patients treated with upfront PBP (8.6%;2 recurrences in 13 patients), p=0.09. In addition, only one patient had to resort to surgery. When analyses according to the BP. used, the recurrence rate was 4.0 times higher for PCT (34.7 vs. 8.6% recurrences), although without reaching statistical significance (p=0.16). Conclusion(s): The PBP is a simple, safe and effective technique for the treatment of NPE during the COVID-19 pandemic, in our series it was associated with a lower recurrence rate. Therefore, it could replace PCT in these patients during the COVID-19 pandemic as optimal first line treatment, providing better quality of life and reducing the need for re-interventions. (Figure Presented).
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Sinonasal cancer accounts for roughly only 3% of upper respiratory tract malignancies and generally presents as a primary malignancy. Although extremely rare, the sinonasal cavity is also a known location for metastasis, with 8% of these cases originating from primary breast cancer. When attempting to differentiate primary disease from metastasis, immunohistochemical analyses play a crucial role in reaching the correct diagnosis. To date, there are a handful of reports describing metastasis involving the paranasal sinuses but even fewer reporting primary sinonasal cancer with coexisting primary malignancy. Here we present a case of primary sinonasal adenocarcinoma in the setting of a long-standing history of breast cancer. The patient, a 73-year-old female, was diagnosed with T1cN1aM0, progesterone receptor positive and estrogen receptor negative ductal carcinoma in situ of the left breast in November 2019. She subsequently underwent bilateral mastectomy and treated with 3 cycles of chemotherapy and anastrozole, which were both discontinued due to intolerance. Of note, in March 2019, MRI of the head incidentally found a 3 x 2 cm mass in right nasal cavity extending into ethmoid sinus. One year later, she presented with mild right sided nasal obstruction and drainage, and biopsy revealed squamous and respiratory mucosa with chronic inflammation. The patient elected to cancel initial surgical resection of the mass due to the COVID-19 pandemic. The patient returned in March 2022 with complaints of eye pressure, double vision, headaches, and worsening nasal obstruction. PET/CT scan was negative for distant metastasis but demonstrated increased uptake in sinus cavity. MRI showed a larger 5 x 3.7 cm mass impressing on medial inferior margins of orbit. Imaging also suggested evidence of dehiscence of lamina and irregular neo-osteogenesis of the skull base. She underwent approach and resection of the mass with histology demonstrating a well differentiated, low grade non-intestinal mucinous adenocarcinoma. Immunohistochemistry was positive for pankeratin and CK7, favoring a primary sinonasal origin. It was estrogen receptor negative and negative for GATA3, a sensitive and fairly specific stain in mammary carcinoma. Adjuvant radiation was recommended postoperatively, however the patient declined this therapy. This case highlights the role of immunohistochemistry to discriminate a new primary cancer from metastasis in patients with a history of breast cancer. Clinically, patients with sinonasal metastasis can present with symptoms ranging from unilateral nasal obstruction, facial pain, diplopia, and decreased vision. On imaging, suspicion of malignancy is raised when there is evidence of destruction of bony boundaries and invasion of surrounding tissues such as the orbit and anterior skull base, as found in our patient. Notably, metastasis to the paranasal sinuses can mimic a primary cancer of the nasal cavity, with both tumors showing epithelial differentiation. However, primary tumors often show neoplastic changes in the overlying respiratory epithelium and do not express estrogen receptor, progesterone receptor, or HER2 positivity, which are known to be correlated with breast cancer. In this setting, GATA3 and estrogen receptor negativity allowed us to diagnose primary nasal cancer more confidently. Therefore, clinicians should be aware of metastatic disease and expand immunohistochemistry panels when appropriate.
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Background: In response to the COVID-19 pandemic, our radiation oncology department was forced to rapidly integrate telemedicine into its practice. While there has been investigation into the implementation, effectiveness, cost, and perceptions of telemedicine, the environmental impact of telemedicine within radiation oncology has not yet been established. This is particularly relevant as climate change is recognized as one of the largest threats to human health, including oncologic outcomes. Yet, the healthcare sector significantly contributes to global carbon emissions, in part due to patient travel. Objective(s): The aim of this study was to assess the impact of telemedicine on travel-related greenhouse gas (GHG) emissions for a large, academic radiation oncology outpatient clinic located in a densely population suburban setting. Method(s): All in-person and telehealth visits over a consecutive 7-day period in June 2021 scheduled at our main outpatient clinic were retrospectively reviewed. Care visits with patients who resided outside of the state were excluded. Travel distance for in-person visits and miles saved for virtual visits was estimated based on patients' reported home address in the electronic medical record. Associated GHG emissions were calculated with the Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation tool (https://greet.es.anl. gov) using a well-to-wheel model, which accounts for all emissions related to fuel (ie. gas, electricity) production and use. Gas, hybrid, plug-in hybrid, and electric vehicle utilization were accounted for per published statewide vehicle registration statistics. GHG emissions were converted into carbon dioxide equivalents (CO2e) using 100-year global warming potentials. Result(s): A total of 158 clinic visits were conducted over the time period. Table 1 describes visit type, telemedicine status, and primary cancer site of the included patients. Total miles traveled for in-person visits was 5,775 miles and an estimated 13,892 potential miles saved were attributed to telemedicine visits. On average, 118 travel miles were saved per telemedicine visit (CO2e, 55 kg). The forecasted annual savings of CO2e attributed to telemedicine visits is 339 metric tons, the equivalent emissions of 61.6 homes' electricity use for one year. Conclusion(s): The integration of telemedicine within a radiation oncology outpatient clinic reduces the environmental impact of patient care. Telemedicine should be considered where feasible and appropriate to establish and promote environmentally sustainable practices within the field.
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Aim: Immune checkpoint inhibitors (ICIs) have been shown to prolong survival in patients that have locally advanced stage III/IV and metastatic non-small cell lung cancer (NSCLC). The role that salvages surgery plays in persistent localised disease and unresponsive synchronous cancer following treatment with a course of ICIs is not yet fully clear. We present a case series of nine patients with stage III/ IV NSCLC that underwent surgical resection after treatment with the ICI, pembrolizumab. Method: Six cases underwent salvage surgery after downstaging of the primary cancer following pembrolizumab treatment and three patients had resection of contralateral lung nodules that were unresponsive to ICI therapy. Three of the cases were open thoracotomies, 3 were robotic-assisted and 2 were video-assisted. One case was converted to open due to pulmonary artery involvement. Results: There was complete, successful macroscopic resection in all cases with each showing histological evidence for active cancer cells. One patient died of COVID pneumonitis in the community within 60 days of surgery. All other patients are alive with no evidence of localised disease or of any disease reoccurrence within 3-18 months of their surgery. Conclusions: Our case series demonstrates the potential for salvage pulmonary resection in select patients with advanced stage NSCLC who have persistent localised disease or unresponsive synchronous cancer after treatment with the ICI, pembrolizumab. Salvage surgery in this group of patients is safe and pragmatic despite high levels of post-immunotherapy hilar fibrosis. Further studies will be required in order to assess overall survival rates.
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Background: Hospitalizations during cancer treatment are common, can impact quality of life and the progress of the treatment. We aimed to investigate the main causes of hospitalizations and factors associated with in-hospital mortality for patients receiving chemotherapy. Methods: This retrospective study included patients (pts) with solid tumors, who received outpatient chemotherapy in the 30-day period before unplanned admission to a cancer center in Brazil, from February to December of 2021. Patients with COVID-19 diagnosis were excluded. We retrieved clinical and laboratory data from health records. Logistic regression univariable and multivariable models were performed to analyze the association of the variables and in-hospital mortality as dependent outcome. Results: 784 pts were included, median age at hospitalization was 60 (IQR 49-68), and 57% were female. Most patients had ECOG 0-1 (61%) and nearly 70% had metastatic disease at admission. The most common primary tumors were colorectal (21.6%), breast (20.1%), lung (8.6%), and gastric (8.6%). Over half (56%) received platin-based regimens, usually in association with fluoropyrimidines or taxanes. Pain (33%), nausea (23%) and fever (16%) were the most referred symptoms at admission. The main diagnosis at were infection (32%), followed by disease progression (DP) (29%), and chemotherapy associated toxicity (26%). A total of 174 (22%) pts required intensive care unit support during hospital stay. The in-hospital overall mortality rate was 18%. Univariable analysis revealed poor ECOG-PS, grade 3 anemia, grade 3 thrombocytopenia and DP associated with in-hospital mortality. In the final multivariable model, ECOG ≥ 2 (OR 1.99, CI 95% 1.33 - 2.99, p <0.001), DP (OR 4.62, CI 95% 3.07 - 7.00, p <0.001) and grade 3 anemia (OR 2.38, CI 95% 1.45 - 3.87, p<0.001) remained statistically associated with in-hospital mortality. Conclusions: A substantial percentage of unplanned admissions after chemotherapy treatment are due to toxicity. Poor performance status, progression of disease on admission and severe anemia are associated with worse in-hospital prognosis. Grade 3 anemia on admission was the only toxicity associated with in-hospital mortality. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: R.C. Bonadio: Personal, Expert Testimony: AstraZeneca, Ache;Personal, Research Grant: Novartis;Personal, Roche. All other authors have declared no conflicts of interest.
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Background: Immune Checkpoint Blockade (ICB) is moving from metastatic to curative setting in different diseases including NSCLC. While for metastatic disease radiological endpoints are currently the standard surrogate marker of benefit from ICBs, based on RECIST or PERCIST criteria, in neoadjuvant setting they often underestimate the response and then pathological response (PR) criteria were developed to evaluate Major PR (MPR), defined as ≤10% viable tumor cells after neoadjuvant treatment, and PR, defined as less than 50% residual tumor cells. Anyway, a non-invasive approach to determine the response to treatment is still an unmet need. Methods: PRINCEPS was a phase 2 clinical trial including limited-stage (IB-IIIA) NSCLC patients who received one administration of atezolizumab before surgery. 18-F FDG PET was performed within 28 days and after 15-22 days from atezolizumab. Surgery was performed at day 22-29 from atezolizumab. PET derived parameters including MTV and TLG was extracted by experienced nuclear physicians. Results: 30 patients were enrolled, all received A and underwent surgical resection after a median of 23 days. MPR was identified in 4, pPR in 8 tumors. Paired PET were available for 28 pts. Mean time from A to PET was 18 days (IQR 3.5). Total TLG and MTV reduction was not correlated with percentage of pPR (p=0.117 and p=0.843, respectively). Reduction of MTV (Pearson correlation 0.509, p=0.006) and TLG (Pearson correlation 0.562, p=0.002) in the primary tumor were strongly correlated with pPR, while no correlation was observed between percentage of pPR and variation in tumor diameters by RECIST criteria (-0.24, p=0.2) nor metabolic response (-0.12, p=0.55). The appearance of metabolically active hilar and mediastinal, non-pathological lymph nodes (LN) was noted in 12/28 patients, and specifically in. 2 out of 4 MPR and 5 out of 8 pPR. A trend toward an higher pPR was observed with LN appearance (mean 52% reduction in pts with LN appearance vs 29% without, p 0.061), probably reflecting immune activation. LN appearance was associated with hyperplasia and histiocytosis in resected, non-metastatic LNs. Conclusions: PET is able to early detect tumor response in localized NSCLC patients treated with ICBs in neoadjuvant setting. Clinical trial identification: NCT02994576. Legal entity responsible for the study: Institut Gustave Roussy. Funding: Roche. Disclosure: N. Chaput-Gras: Financial Interests, Personal, Advisory Board, Strong-Iopredi Scientific Advisory Board: AstraZeneca;Financial Interests, Institutional, Invited Speaker, Educational Session On Immune Cell Death: Servier;Financial Interests, Institutional, Expert Testimony, Expertise On Immune Cell Death Biomarkers: Servier;Financial Interests, Personal, Invited Speaker: Cytune Pharma;Financial Interests, Institutional, Research Grant, Research grant to identify immune biomarkers associated to clinical response in patients treated with agonistic mAbs: GSK;Financial Interests, Institutional, Research Grant, Preclinical studies in mice: GSK;Financial Interests, Institutional, Research Grant, Immune profiling of Head & Neck tumors: Sanofi. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen;Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen;Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre;Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Resea ch Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, MSD, Boehringer-Ingelheim;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi;Financial Interests, Personal, Expert Testimony: Ose Immunotherapeutics;Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD;Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda;Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Eisai, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. All other authors have declared no conflicts of interest.
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Introduction: It was aimed to evaluate the efficacy, local control and survival in patients with inoperable primary or metastatic lung cancer who underwent stereotactic body radiotherapy (SBRT) using the Cyberknife-M6 (CK-M6) with lung optimized treatment (LOT) module. Methods: Ethics committee (no: 2018-7/6) and scientific research project (OUAP (T) 2019/1) approval were obtained. 23 lesions of 21 patients were treated between April 2019 to December 2020 at our department. The patients were immobilized in the supine position by wearing a Synchrony vest, with the hands at their sides. A planning 4D-CT was obtained in a free breathing modality. The gross target volumes was created both on the full-inhale and full-exhale phases and internal target volume (ITV) was created. By taking an image of patients on the treatment device, tracking modality was selected according to the visibility of the target. Zero-View tracking was applied in 10 patients, 1-View in 10 patients, 2-View in 1 patients. 3 to 5 mm margin added for planning target volume (PTV) according to tracking method. Median ITV and PTV was 9,38 (2-52,34) and 20,27 (9,25-82,7) cc, respectively. An InCise2 multileaf collimator optimized by the Monte Carlo algoritm was used in all patients. A pair of the orthogonal kV X-ray imaging systems were used for simultaneous target tracking. Median prescribed dose was 48 Gy in 4 fractions (30-54 Gy in 3-6 fractions) administered consecutively or every other day. Prescription isodose covering 95% of PTV was 82,5% (77,4-99,3). Median conformity and homogeneity index was 1,17 (1,02-1,77) and 1,22 (1,09-1,29), respectively. Median BED10 was 100 Gy (53,62-151,2) and median beam on time was 26 minutes (12-42). Results: Patients were evaluated on January 2022. The median follow-up was 21 months (2-33). The median age was 68 (53-80) and 40% of the cases were adenocarcinoma. Two patients diagnosed with radiologically. Median lesion size was 13 mm (9-27). SBRT was applied to 13 primary tumors, 3 lung metastases and 7 lymph nodes. At initial evaluation, complete, partial and stable response was found 30%, 65% and 5%, respectively. During the follow-up, 3 patients locally recurred at a median of 11 months (9-14). The median and one-year local recurrence free survival was 22 months, and 89%. Acute and late grade 1-2 pulmonary complications was seen in 10 patients in a median of 7 months (2-13). While the cause of death in 6 cases was existent cardiac morbidity, covid19 pneumonia, lung infection (2) and progression (2), it was unknown in 1 patient. The median and one-year survival was 23 months and 95%. Conclusions: LOT module of the CK-M6 Xsight lung tracking system allows for the application of fiducial-free motion management strategies. The advantage of our study is that the most appropriate tracking modality can be selected prospectively before treatment. In our study, excellent local control with a median survival of 23 months for primary and metastatic lung cancer. With a median treatment time 26 minutes, noninvasive CK-M6 based SBRT was efficient, safe and comfortable treatment in lung cancer. Keywords: lung cancer, Cyberknife-M6, stereotactic body radiotherapy
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Introduction: The COVID-19 pandemic led to worldwide barriers to access to operating rooms;some multidisciplinary thoracic oncology teams pivoted to a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to provide radical-intent treatment combining immediate SABR followed by planned surgery when surgical resource constraints ameliorated. This pragmatic approach, termed SABR-BRIDGE, was instituted with prospective data collection at four institutions (3 Canada, 1 USA);herein we present the surgical and pathological results from this approach. Methods: Eligible participants had early-stage presumed or biopsy-proven lung malignancy that would otherwise be surgically-resected. SABR was delivered using standard institutional guidelines with one of three fractionation regimens: 30-34 Gy /1 fraction, 45-55 Gy/3-5 fractions, or 60 Gy/8 fractions. Surgery was recommended at a minimum of 3 months following SABR with standardized pathologic assessment of resected tissue. A pathological complete response (pCR) was defined as absence of viable cancer, and a major pathologic response (MPR) was defined as ≤10% viable tissue. Results: Seventy-five participants were enrolled, of which 72 received SABR. Following SABR, 26 patients underwent resection, while 46 did not;reasons for not undergoing surgery included metastasis (n=2), non-cancer death (n=1), awaiting lung surgery (n=13) and patient choice given favorable post-SABR imaging response (n=30). Of 26 patients who underwent resection, 62% had a pre-treatment biopsy. The most common SABR regimens were 34 Gy /1 fraction (31%) and 48 Gy in 3-4 fractions (31%). SABR was well-tolerated, with two grade 1 toxicities (pain, 7.7%), and one grade 3 pneumonitis (3.8%). Median time-to-surgery was 4.5 months from SABR completion (range:2-17.5 months). Most had minimally-invasive surgery (n=19, 73%) with 4 patients (15%) requiring conversion to thoracotomy, and 3 (12%) had planned open operation. Surgery was reported as being more difficult because of SABR in 38% (n=10). There were two intraoperative complications (7.7%, pulmonary artery injury), and 8 patients with post-operative complications (31%, all grade 2, most commonly air leaks [n=5]). The amount of residual primary tumor ranged from 0% to 90%. Thirteen (50%) had pCR while 19 (73%) had MPR. Rates of pCR were higher in patients operated upon at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months). Rates of pCR were higher in patients without pre-treatment tissue diagnosis (91% versus 20% in those without and with tissue diagnosis, respectively). In 31% (n=8) of patients, nodal disease was discovered on resection, with half being N2 (4/26=15%). Conclusions: The SABR-BRIDGE approach allowed for delivery of treatment with minimal upstaging during a period of operating room closure & high risk for patients. Surgery was well-tolerated. However, most patients who received SABR did not proceed to surgery, limiting precise estimates of pCR rates. However, the reported pCR rate is consistent with previous phase II trial data. Keywords: lung surgery, SBRT, Multi-modal therapy
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Background: Some known viral infections can lead to a diagnosis of cancer (e.g: HPV, HIV, EBV, etc.) Anecdotical reports of a Covid 19 infection, and the subsequent diagnosis of a new cancer have been mentioned by few patients (pts). This relationship has not yet been fully documented. Covid 19 infected persons have been identified to have a suppressed adaptive immunity, which one of its principal functions is to maintain occult cancer cells in an equilibrium state. We studied the possible role of a Covid 19 infection and the subsequent diagnosis of a new primary cancer happening during the Covid pandemic (01/2020 - 12/2021). A survey was sent to all new members of Belong.life, a free and anonymous global cancer app for pts and their caregivers. This study took place prior to the omicron variant surge. Methods: 2579 Belong.life members received randomly, in the app various cancer groups, a 10 questions voluntary survey regarding the onset of a Covid 19 infection and the development of a subsequent new primary cancer diagnosis. 262 replied of whom 124 fulfilled the eligibility criteria and confirmed having had a Covid 19 infection followed by a new cancer diagnosis. Data on the 124 pts was analyzed by Belong analysts, according to age, sex, geographical distribution, Covid 19 infection onset and type and timing of the cancer diagnosis. Results: Most pts were USA based (102/124, 82%), and 1/3 were < 49 years, followed by a 1/3 in the 50-59 and > 60 groups. 71% (88/ 124) were females. All had a prior Covid 19 infection and only 14 (11%) required hospitalization. 109/124 (88%) had a primary cancer diagnosis and 15 (12%) had disease recurrence. Breast cancer was diagnosed in 38% (47/124), followed by lung and gynecological cancers (10/124, 8% respectively). Time from Covid 19 infection to primary cancer diagnosis was < 6 months in 57 /124 (46%) and 6-12 months in 40/124 (32%). Breast cancer developed earlier (< 12 months) in 87% of the pts. In total 97/124 (78%) pts had their disease diagnosed within less than a year. Conclusions: Known viruses might precede the onset of a new cancer. The role of corona viruses and subsequent development of a cancer is unknown. Adaptive immunity maintains occult cancer cells in a steady state, while a Covid 19 infection interferes with it, causing a weak and delayed immune response, which could be responsible, after a period, for the onset of a new primary cancer. We are presenting RWD on 124 pts with new primary cancers diagnosed after a Covid 19 infection. This represents a 5% incidence in a random pts group (124/2579) as described above. Further studies should be planned to investigate this real world increased incidence and testing of the diverse immune parameters are also warranted to further understand the intersection pathways of Covid 19 infection and cancer development.
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Background: The utilization of virtual second opinions in oncology has increased considerably in the last decade, driven by the increased complexity of care and desire for expert opinion, improved technologies in telemedicine, and the acceleration of virtual services due to the Covid-19 pandemic. Therefore, it is important to further understand the patient populations that currently use virtual second opinion programs and to measure their effectiveness. Virtual second opinion programs provide a platform for patients to submit their medical history and questions regarding their condition to remote specialists who then render their opinions on diagnosis and management. Currently there is a paucity of research on the types of patient populations that seek second opinions and the outcomes of these rendered opinions. Here we describe the patient characteristics and changes in management associated with utilization of a virtual second opinion service at an academic medical center. Methods: In this IRB-approved retrospective review, we identified 657 cancer patients that utilized a virtual digital health platform to engage in second opinions at Stanford Healthcare. Patient demographics, cancer staging, site of origin, and prior therapeutic and surgical history were collected. Physician opinions rendered were self-classified into “major change in treatment”, “minor change in treatment”, or “no change in treatment.”. Results: The majority of patients who utilized the virtual second-opinion platform had a diagnosis late-stage cancer (with 77.2% at Stage III or IV). Breast cancer was the most common primary tumor site (24.7% of patients) followed by GI (21.9%) and GU malignancies (14.0%). Patients diagnosed with dermatological (4.4%), head and neck (3.3%), and neurological (3.2%) malignancies were least common. Physicians providing the virtual second-opinion were primarily medical oncologists (67.6%), followed by gynecologists (6.8%), urologists (5.2%), radiation oncologists (5.0%), and surgical oncologists (4.4%). Physicians self-reported that in more than half of cases reviewed (53.8%) a minor or major treatment change was recommended. Conclusions: This study showed that patients access second opinion platforms at late stage of cancer disease progression. With treatment changes recommended for more than half of the cases, virtual second opinion programs can potentially have a significant impact on cancer care. Patient satisfaction and clinical outcomes from virtual second opinion programs is an area of on-going research.
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Background: Few cases of digital ischemia and gangrene associated with primary solid tumors have been described in literature[3]. The exact mechanism of severe occurrence has not been completely understood and the available treatment options have an extremely limited utility [1,2].In the most cases the patients were elderly women with adenocarcinomas of digestive or gynaecologic apparatuses [4]. Objectives: We describe a new case of digital gangrene as unusual presentation of ovarian cancer in a 36 years old woman. Methods: 36 years old female was admitted to our Reheumatology deparment with blackish Blackish discoloration of the toes of one week duration. She had history of COVID-19 infection 8 months prior to the presentation then developed hemoptysis, picture suggestive of ILD, generalized anasarca and skin rash;accordingly an initial diagnosis of post COVID-19 vasculitis was made by dermatologist. The blood tests were ESR:21 mm/hr, CRP:25.7, D.Dimer:8.8, Ferri-tin:575 ng/ml, lymphopenia:0.9, S.Creatinine:2, 24 h urinary protein: 325 mg/24h and all autoimmune markers were negative except anti nuclear antibody (ANA) with titer:1/160. Further assessment revealed that she had multiple site coag-ulopathy;internal jugular vein thrombosis, bilateral lower limbs Deep Venous Thrombosis (DVT). Neck ultrasound surprisingly showed bilateral enlarged suspicious looking supraclavicular lymph node with lost hilum which was Biopsied for histopathological correlation which revealed focally necrotizing adenocarci-noma with signifcant signet ring differentiation. Searching for the primary malignancy, tumor markers were sent CA125: 584 u/ml (up to 35), Pelvi-abdominal Magnetic resonance imaging (MRI) revealed Left ovarian mass measuring 3.6 x 3.4 x 4.4 cm highly suspicious of malignant neoplastic growth for histopatho-logical correlation, Suspicious looking pelviabdominal lymph nodes mostly representing malignant lymphadenopathy, Scattered peritoneal nodules suspicious of metastatic deposits. Results: During admision the patient received full dose anticoagulation (Low Molecular Weight Heparin: 60 iu/12 h). Upon diagnosis we arrange the transferal to the oncology department to continue her management plan. Unfortunately;the case was terminal for palliative therapy and she died after 2 weeks. Conclusion: Bluish discoloration of digits and toes may be a clue for diagnosis of many diseases not only vasculitis. Malignancy can disturb the immune system in a way that mimic any systemic connective tissue disease. Acute insult aggressive multiple site deep venous thrombosis (DVT) necessitate thinking outside the box and consider other causes of coagulopathy like visceral malignancy.
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Background: The risk of developing COVID-19 in patients with cancer has increased, directly influenced by age and the magnitude of comorbidities. In this population, the estimated mortality is 10.9%. With this, the urgent need for patients with cancer to get vaccinated against SARS COV 2 has generated an international response. With the ongoing vaccination campaign, experts in nuclear medicine have observed an increment in lymph node uptake in PET CT with 18 FDG. Increased uptake in lymph nodes in patients with a neoplastic diagnosis on PET CT 18 FDG must be closely followed and well-studied to differentiate disease progression from an inflammatory, fleeting reaction. Methods: Amongst the inclusion criteria were patients over 18 years of age with solid tumors, including lymphomas, who were on active oncologic treatment with chemotherapy, immune therapy, radiotherapy or under surveillance between April 2021 and July 2021 who underwent a PET CT scan and had at least one dose of a COVID 19 vaccine, and a prior PET CT to the vaccine for comparison. Patients were excluded who showed evidence of progression or disease recurrence of the primary tumor. We evaluated lymph node size and metabolism measured by SUV max in the PET CT scan prior to being vaccinated and posterior to, as well as patients' clinical characteristics. Results: A total of 92 patients who met inclusion criteria were included in the study. Amongst those, 54.3% were women, the median age was 68 years (27 - 95 years), the most common neoplastic diagnoses were breast cancer (19.6%), gastrointestinal tumors (17.4%), urothelial tumors (9.8%), lymphomas (9.8%) and ovarian cancer (8.7%). 52.2% of patients were under surveillance and 47.8% were under active treatment. 79% of patients had at least 2 vaccine doses. 59% had received Pfizer vaccines and the measurable adenopathies were axillary in 32.7% and mediastinal in 27%. The medium size of the measured lymph nodes prior to receiving the vaccine was 2.86 mm with an SUV max of 1.24, while after vaccination were 6.01 and 2.27 respectively. A Kruskal Wallis test was conducted to compare median results according to histopathologic reports, with no statistical difference. A Mann Whitney U test was conducted to compare breast cancer to other cancer histologies, where a statistical difference was found for SUV max, p = 0.003 and size with p = 0.033. Conclusions: This work details significant differences between lymph node size and SUV max in oncologic patients pre and post vaccination for COVID 19, showing a statistical difference in patients with breast cancer. This increment in lymph node uptake in patients with a neoplastic diagnosis PET CT 18 FDG must be closely followed and well-studied to differentiate disease progression from an inflammatory reaction.
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Background: CRC still is one of the leading causes of cancer related death though prognosis has improved through guideline based management. The COVID-19 pandemic lead to re-allocation of resources subordinating all sections of care for CRC patients. We present data on changes of CRC care during the pandemic from 22 German AIO CC and our high volume Institute of Pathology (pathology). Methods: Data was collected retrospectively comparing the months (mo) of the first wave (fw) (4-6/2020) and second wave (sw) (11-12/2020) of the pandemic with corresponding periods (cp) in 2019 focusing on the number of precancerous (ICD-O/0+2) and malignant (ICD-O/ 3+6) colorectal lesions (CRL) diagnosed by our pathology, the number/stage of primary diagnoses (PD) and the number of surgeries (surg) at AIO CC. There, quality criteria of CRC care were also assessed (number of PD discussed within a multidisciplinary tumor board (tb), received social service (soc)/ psychological (psy) counseling or recruited into a clinical trial). Statistical analysis was performed using students t-test for paired data. Results: Numbers of CRL detected upon histology (row 1-3), number of cases, surg and quality criteria from AIO CC (row 4-9) are displayed in the table. We saw a dip in diagnosed CRL and number of surg (p=0.007) only during fw, whereas PD dipped significantly in both waves. A significant reduction in diagnosis of stage III CRC was detected for 2019 vs. 2020 (p=0.001), not for other stages. Quality criteria showed a significant reduction in clinical trial inclusion, a small dip in soc/psy counseling and persistently high tb presentation. Conclusions: We detected a significant decrease of premalignant lesions and primary cancers during the first year of the pandemic which may impact cancer mortality in the future. Certified German CC provided CRC care with significant reduction in clinical trial inclusion only, suggesting high stability of established certified cancer care infrastructure.
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Background This project analysed the Integrated Palliative Outcome Scale (IPOS) in a 20-bedded in-patient unit during the COVID-19 Pandemic. The scores were taken at admission, at change in Phase of Illness and at point of discharge or death. These scores were used to monitor symptom progression and effectiveness of management during the COVID-19 pandemic. Methods The Electronic patient record (EPR) identified 110 hospice inpatients, from a total 141 admissions between 1st October 2020 - 31st March 2021) who had at least one IPOS recorded. Initial and subsequent IPOS scores were inputted and analysed in Microsoft Excel and baseline symptom prevalence and outcome measures reported (bar charts and radar plots). Results Over the 6-month period analysed 93% of patients admitted had a primary cancer diagnosis and 7% non-cancer related conditions. The worst rated physical symptoms on admission included;weakness (2.67), poor mobility (2.59) and poor appetite (2.27). Family worry was the top score of all the domains with an average initial admission score of 3.13, this is not unsurprising, and likely that the visiting restrictions in place will be contributing to this domain All physical symptoms were successfully reduced from start to end of admission except for impact of drowsiness. The greatest reductions in average scores of the physical domains were seen for constipation (28.6%), Nausea (23.9%) and Weakness (17.2%). However, average scores for anxiety, depression and sharing feelings rose by 2.3%, 10.5% and 5.7% during the admission. Conclusions This work confirms that an in-patient unit can collect and analyse patient outcomes data, even during a pandemic. The results demonstrate the positive impact that admission to a hospice can have on the symptoms of terminally ill patients, especially physical symptoms. For us it has highlighted areas of improvement especially psychological and spiritual care.