ABSTRACTS

Opinions of lung cancer patients on tobacco advertising and smoking in public places

Background

Non-smokers favour restrictions on cigarette advertising and restrictions on smoking in public places. It might be anticipated that lung cancer patients, faced with the dire consequence of their smoking, might also be relatively hostile to cigarette advertising and smoking. To our knowledge such a difference in opinion has not previously been studied. We surveyed the opinions of lung cancer patients (the cases) and compared them to those of members of the general population (the controls).

Methods

Each of the 46 lung cancer cases had been seen by one of the participating physicians, and the 468 controls were drawn as a random sample from the general population of Luxembourg. For cigarette advertising, subjects were asked if they approved the banning of advertising for each of 7 sites or media: newspapers, magazines, television, radio, sports grounds, near schools, and hoardings. The dependent variable thus ranged from 0 (no ban approved) to 7 (ban approved for all sites and media). For smoking in public places, subjects were asked if they approved of the banning of smoking in each of 10 locations: schools, public services and enterprises, shops, restaurants, cinemas, doctors’ waiting rooms, railway stations, public transport, and meetings. The dependent variable thus ranged from 0 to 10.

Results

Cases were significantly against cigarette advertising for an average of 1.9 more sites out of 7 than the controls (ANOVA, P=0.0015). Non-smokers favoured a ban on advertising for an average of 1.5 more sites than smokers (P=0.0048). For smoking in public places, the cases approved more restrictions than controls (average difference 1.1 locations out of 10, P=0.0326) and non-smokers approved more restrictions than smokers (P=0.0046). There was no significant effect of age, sex or other variables.

Conclusions

The results showed a clear order of subjects’ hostility to cigarette advertising and smoking in public places: lung cancer patients > non-smoking controls > smoking controls. This is remarkable since almost all the cases were current smokers or recent ex-smokers. Thus the diagnosis of lung cancer in a smoker seemed to shift his or her attitude against smoking practices.

Neuroendocrine neoplasms grade 3: prospective overall survival data and survival after platinum-etoposide chemotherapy within an ENETS Center of Excellence

Introduction

Overall survival (OS) and progression-free survival (PFS) data of grade 3 NENs remains limited.

Aim

The aim is to report prospective survival data in grade 3 NENs treated within NETwerk.

Methods

Patient characteristics of all grade 3 NENs treated from April 2016 to May 2018 were prospectively recorded. Median OS (mOS) from diagnosis and mOS and median PFS (mPFS) after start cisplatinum/carboplatinum-etoposide chemotherapy was calculated.

Results

Of 79 included NEN grade 3 patients, there were 46 males (58,2%). Mean age at diagnosis was 68 years [range 22-90y]. In 67% (N=53) of the cases, the primary tumor was a GEP-NEN (of which 18 unknown). In our population 44% (N=35) had metastases at diagnoses, 44% (N=35) had a Ki67 index ≥ 55%, 30% (N=24) had a Ki67 index < 55%. Platinum-etoposide chemotherapy was given in 29% (N=23) of the patients. The majority (N=41) had FDG-PET imaging of which 36 were positive and 14 had somatostatin receptor imaging (SRS) of which 11 were positive. Combined FDG-SRS positivity was seen in 5 of 11 patients (45%). Overall mOS was 10.5m (95%CI: 6.6-NR). In GEP-NEN mOS was 8.3m (95% CI: 6.0-18.7), while in NENs from other origin mOS was 12m (95% CI: 6.8-NR, p = 0.2). The mOS for patients with a Ki67 index < 55% was 14.2m (95% CI: 8.9-NA) vs 8.2m (95% CI: 5.6-NA) for patients with Ki67 index ≥ 55% (p=0.3). In multivariate analysis, age at diagnosis had significant impact on OS (HR 0.95, p=0.003), while tumor origin showed trend towards significance (HR 0.49, p= 0.056). The mPFS and mOS after chemotherapy were 6.5m (95%: 4.8 -NR) and 14.2m (95% CI: 8.3-NR). For the chemotherapy-treated group no significant effect of tumor location, metastasis at diagnosis and age at diagnosis was seen on OS and PFS.

Conclusions

In this grade 3 NEN cohort, non-GEP-NENs have a better OS survival than GEP-NENs. Our results confirm the limited PFS and OS after platinum-etoposide chemotherapy in grade 3 NENs, highlighting the need for better treatment. When performed, FDG-PET and SRS-positivity is frequent and could guide treatment.

FGF- R inhibition, a biomarker driven alternative in second line metastatic urothelial cancer

Introduction

Fibroblast growth factor (FGF) signaling contributes to tumorigenesis in a wide variety of tumor types. In metastatic urothelial cancer (mUC), mutations of the FGF receptor can be found in about 20% of cases. This abstract discusses two phase III trials currently recruiting UC patients in Belgium using the FGF-R targeting agents rogaratinib (BAY-1163877) and erdafitinib (JNJ-42756493).

Materials and methods

The protocols of both studies were analyzed to identify targeted unmet medical needs in the treatment of mUC.

Results

Erdafitinib is a strong pan-FGF-R inhibitor that showed significant inhibition of proliferation in preclinical trials. In a large phase I study (N=187) of mUC patients with FGF-R aberrations, overall response rate (ORR)was 40%, 70% in higher doses. The most frequent adverse events (AE) were hyperphosphatemia, dry mouth, asthenia and stomatitis. The current randomized open label phase III trial(NCT03390504) compares single agent erdafitinib to chemotherapy (investigators choice) in patients with prior anti-PD(L)1 treatment in one cohort and to pembrolizumab in patients without prior anti-PD(L)1 treatment in the second cohort. The primary endpoint is overall survival (OS).

Rogaratinib is a strong pan-FGF-R targeting TKI that also showed strong inhibition of cell growth in preclinical models. Two phase I trials have studied rogaratinib. Tolerance was good with hyperphosphatemia, fatigue and gastro-intestinal symptoms as main AEs. As with other FGF-R inhibitors, retinal disorder is a treatment limiting toxicity. The current open label study randomizes mUC patients to rogaratinib and second line chemotherapy (docetaxel, paclitaxel or vinflunin) in patients with tumors expressing FGF-R mutations or high mRNA load. The phase II part will randomize 58 patients in each arm, the study is planned to continue in a phase III after a futility analysis. Primary endpoint in phase II is ORR, in phase III OS.

Conclusions

Treatment of mUC patients after progression on platinum based chemotherapy and eventually checkpoint inhibitors is an unmet need. Both rogaratinib and erdafitinib are effective in targeting FGF-R mutations in a subgroup of patients and have shown high ORR in phase I studies. Phase III trials are open to recruitment and offer mUC patients a biomarker-based alternative to poorly active second line cytotoxic therapy.

The safety of anti-PD1 therapy in a case of paraneoplastic immune disease: a case report

Cancer-associated thrombotic microangiopathy is a group of disorders defined by microvascular thrombosis, thrombocytopoenia and ischaemic end-organ damage. Rarely, it may be a manifestation of the malignancy itself or a side effect of its therapy.

We report on a 64-year-old male, diagnosed in 2017 with a T1N1M0 squamous cell carcinoma of the pyriform sinus treated by radio-chemotherapy (cisplatin + 70 Gy). The patient was hospitalised six months after the completion of the treatment, while he was still in complete remission, for fatigue and an altered general status. Laboratory results revealed haemolytic anaemia, thrombocytopenia, a negative coombs test, LDH 537, undetectable haptoglobin and acute renal insufficiency requiring haemodialysis. Investigations showed presence of schistocytes, a normal ADAMTS13 activity and absence of ADAMTS13 inhibition. A kidney biopsy confirmed the diagnosis of thrombotic microangiopathy and plasmapheresis was initiated which lead to a partial resolution of the thrombocytopenia and other microangiopathy factors. A PET-CT scan revealed multiple secondary lesions in the lungs along with the lymph nodes. A lymph node biopsy was performed and showed metastatic squamous cell carcinoma which confirmed the probable paraneoplastic nature of the disease. We conducted a literature review that revealed that when the thrombotic microangiopathy is cancer-associated it is necessary to treat the underlying disease. It was therefore decided to discontinue the plasmapheresis and treat with anti-PD1 antibody therapy (nivolumab). A PET-scan revealed progression after three cycles of nivolumab and we decided to stop the treatment, however we did not observe recurrence of the thrombotic microangiopathy.

Despite the debate about immunotherapy in active autoimmune diseases, this case demonstrates the safety of anti PD-1 therapy in case of a paraneoplastic immune disease.

Renal cell carcinoma with TFE3 rearrangement at Xp11.2

Renal cell carcinoma with TFE3 (Transcription Factor for immunoglobulin heavy-chain enhancer 3) rearrangement at Xp11.2 is a distinct subtype manifesting an indolent clinical course in children, with recent reports suggesting a more aggressive entity in adults. This subtype is morphologically heterogeneous and can be misclassified as clear cell or papillary renal cell carcinoma (RCC). RCCs with TFE3 rearrangement account for only approximately 1% of adult RCCs and may be clinical aggressive tumor.

Herein, we describe the case of a 17-year-old woman who presented for lumbar and abdominal pain for 3 months. Abdominal CT revealed small liver lesions, retroperitoneal lymphadenopathies, lytic bone lesion L3 confirmed by the PET CT Scan.

A biopsy of a retroperitoneal lymph node revealed a clear/granular cell tumor, with psammoma calcifications with diffuse expression of CD10, focal expression of PAX8 suggesting a renal carcinoma associated with the Xp11.2 translocation/TFE3 rearrangement.

Patient was started on Sunitinib and Denosumab with a good response but one year later we documented a progressive disease so that the patient was included in a clinical trial with a VEGF inhibitor and angiopoïetin II inhibitor. Four cycles later, we documented again a progressive disease with peritoneal carcinomatosis and ascitis. Consequently, a third line therapy with nivolumab was started with good partial response but the treatment was stopped because of nivolumab induced hepatitis. The disease kept on progressing and a fourth line with Cabozantinib was prescribed and PET-FDG showed a mixed response. The patient is still receiving Cabozantinib with dose reduction due to toxicity. The natural history of renal-cell carcinoma associated with TFE3 rearrangement at Xp11.2 is not well described because the tumor type is so rare. The question is whether these patients should be treated the same way as RCCs without molecular alteration.

Incidence and prognosis of biliary tract and gallbladder cancers in an academic hospital

Introduction

Biliary tract and gallbladder cancers are rare tumors with a poor prognosis (except ampulla). There is a variation in the evolution of the incidence around the world. According to Belgian Cancer Registry, the number of hepatobiliary cancers increases every year since 2004.

Material and Methodology

A retrospective study was performed. Patients with cholangiocarcinoma, ampulla or gallbladder cancers who were diagnosed at CHU UCL Namur site Godinne between 1997 and 2017 were included in this analysis. The evolution of the incidence was evaluated by the Mann-Kendall method on 7 periods of 3 years. We calculated the survival of these patients by the Kaplan Meier method and we determined prognostic factors by the logrank test.

Results

Between 1997 and 2017, we report an incidence of 128 patients in our center. Twenty percent were ampulla, 77% cholangiocarcinoma including 38% intrahepatic, 16% hilar and 23% extrahepatic. Last 3% corresponded to gallbladder cancer. According to the Mann-Kendall test, the evolution of the incidence of these cancers increases significantly with a slope of Sen of 7 corresponding to 7 additional new cases for each successive 3-year period (p=0.003). Our population consisted of 52% males with an average age of 68.6±11.9 years. Forty-five percent smoked, 14% consumed more than 3 units of alcohol a day, 8% had cirrhosis and 20% were diabetic. Regarding treatments, 34% had surgery, 59% received chemotherapy and 26% only supportive care. The average BMI was 26.4±5.6kg/m². The one-year overall survival was 52.0±4.7%. Poor prognosis factors were age and metastatic disease (p<0.001). The ampulla had a better prognosis with a one-year overall survival of 75.1%±9.8% compared to cholangiocarcinoma intrahepatic, hilar and extrahepatic with respectively 38.0±7.4%, 38.6±12.5% and 51.9±9.6% (p<0.001 for all). Finally, intrahepatic cholangiocarcinoma had a lower progression-free survival than the extrahepatic cholangiocarcinoma with a hazard ratio of 2.33 (p=0.001), however survival was identical.

Conclusion

Incidence of biliary tract and gallbladder cancers increases in our center. Further investigations are needed to determine the reasons for this increase. Although new therapies are emerging, these cancers still have a poor prognosis. Determining risk factors could help to develop preventive approach.

Hemophagocytic lymphohistiocytosis, an unusual initial presentation of a gastric adenocarcinoma with an unusual exclusive bone marrow metastasis

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening condition caused by an excessive chaotic immune activation. It can be primary or secondary to a trigger such as an auto-immune disease, an infectious process or a malignancy. It is usually associated with hematological malignancies and less frequently with solid tumors. This medical emergency has variable presentations lacking pathognomonic clinical and laboratory findings. The prognosis is usually dismal and is associated with high mortality rates.

Here we report the case of a 45-year-old male patient, previously healthy, who presented with alteration of general status and high-grade fever. Laboratory investigations showed a pancytopenia, with grade IV neutropenia, grade II normocytic anemia and grade III thrombocytopenia. The peripheral smear didn’t reveal any abnormal immature cells, schistocytes, nor evidence of leukoerythroblastic reaction. The fibrinogen was low. The bilirubin was increased with a grade III elevation of transaminases and a grade II elevation of cholestatic liver enzymes. The lactate dehydrogenase (LDH) was 10 times more than the upper limit of normal. The ferritin was quite elevated (12598 ng/mL) and there was a hypertriglyceridemia of 750 mg/dL. The clinical and biological findings were consistent with the diagnosis of HLH which was confirmed by a bone marrow biopsy revealing erythro-phagocytocytic changes. There was also a bone marrow infiltration by carcinoma cells; the immunohistochemistry profile was compatible with a gastro-intestinal primary. The radiological and endoscopic investigations concluded for a newly diagnosed gastric adenocarcinoma, initially presenting with exclusive bone marrow metastasis leading to hemophagocytic lymphohistiocytosis. There were no other associated metastatic sites as usually seen in generalized gastric carcinomas. The clinical condition deteriorated despite the urgent initiation of a standard treatment of HLH. The patient passed away after multi-organ failure.

HLH is an aggressive syndrome. Clinicians must be aware of this rare entity that may be the initial presentation of a certain triggering disorder. The treatment consists of stopping the inflammatory cascade via the HLH treatment protocol followed by the appropriate treatment of the underlying trigger.