Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment

BACKGROUND: At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] ≥ 6 months), de novo disease progression (PD) and secondary PD in patients receiving fulvestrant ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC). METHODS: Changes in cancer antigen 15–3 (CA 15-3) and carcinoembryonic antigen (CEA) were prospectively monitored (monthly) and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. RESULTS: In patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165). In patients with SD ≥ 6 months (n = 28 [41.8%]), both CA 15-3 (P < 0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased significantly (P < 0.0001) after 4 months; CEA also increased significantly (P = 0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P < 0.0001) increased significantly in the 3 months preceding secondary PD. CONCLUSION: CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant

Analysis of trastuzumab and chemotherapy in advanced breast cancer after the failure of at least one earlier combination: An observational study

BACKGROUND: Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression. METHODS: Fifty-four patients, median age 46 years, range 25–73 years, were included. We analysed for time to tumour progression (TTP) for first, second and beyond second line treatment, response rates and overall survival. RESULTS: Median time of observation was 24 months, range 7–51. Response rates for first line treatment were 7.4% complete remission (CR), 35.2% partial remissions (PR), 42.6% stable disease > 6 months (SD) and 14.8% of patients experienced disease progression despite treatment (PD). Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3(rd )line, 18 pts 4(th )line, 6 pts 5(th )line, 2 pts 6(th )line and 1 patient 7(th )line) were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m) in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed. CONCLUSION: The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted

Long-Term Swallowing Outcome and Dysphagia in Advanced Staged Head and Neck Squamous Cell Carcinomas after Radiotherapy

Objective: To evaluate the impact of radiotherapy (RT) on dysphagia and long-term swallowing outcome in patients with stage III and IV head and neck squamous cell carcinomas (HNSCCs). Material and Methods: Between 2005 and 2008, 189 patients with HNSCCs underwent primary or adjuvant RT in a curative setting. Long-term swallowing outcome was evaluated in 50 patients. Among them, 26 were further eligible for prospective analysis of long-term swallowing and dysphagia outcome. Medical charts were retrospectively reviewed regarding pre- and post-treatment dysphagia (3 months after last irradiation setting) as well as persisting long-term dysphagia (2019–2021). Results: Pre-treatment dysphagia was observed in 24 (48%) of 50 patients, particularly in oropharyngeal or hypopharyngeal stage III–IV tumors (OR 9.3; p = 0.003). Conversely, 46 patients (92%) complained about post-treatment dysphagic symptoms, which were more commonly seen in patients with positive neck nodes (OR 10.5; p = 0.037). The post-treatment dysphagia rate dropped from 92% to 24% (p p = 0.019), dysgeusia (OR 9.9; p = 0.036) and free flap reconstruction (OR 6.1; p = 0.022). Conclusion: Pretreatment dysphagia is common in advanced stage HNSCCs and almost all patients complain about dysphagia at the end of RT. Importantly, applied RT protocols did not affect long-term dysphagia, which improves significantly in the majority of patients over time. Meeting Information: Preliminary results have been presented at the 65th Annual Meeting of the Austrian Society of Otorhinolaryngology, 22–26 September 2021, Austria

ART for head and neck patients: On the difference between VMAT and IMPT

<div><p></p><p>Anatomical changes in the head-and-neck (H&N) region during the course of treatment can cause deteriorated dose distributions. Different replanning strategies were investigated for volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT).</p><p><b>Material and methods.</b> For six H&N patients two repeated computed tomography (CT) and magnetic resonance (MR) (CT₁/MR₁ at week 2 and CT₂/MR₂ at week 4) scans were acquired additionally to the initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV_70Gy, CTV_63Gy, CTV_56Gy) were delineated on MRs and transferred to respective CT data set. Simultaneously integrated boost plans were created using VMAT (two arcs) and IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were replanned on the repeated CTs. A Demon algorithm was used for deformable registration of the repeated CTs with the initial CT and utilized for dose accumulation. Total dose estimations were performed to compare ART versus standard treatment strategies.</p><p><b>Results.</b> Dosimetric evaluation of recalculated plans on CT₁ and CT₂ showed increasing OAR doses for both, VMAT and IMPT. The target coverage of recalculated VMAT plans was considered acceptable in three cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced D_2% for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular patients. These D_2% reductions were reaching 9 Gy and 14 Gy for the spinal cord. ART improved target dose homogeneity, especially for protons, i.e. D_2% decreased by up to 8 Gy while D_98% increased by 1.2 Gy.</p><p><b>Conclusion.</b> ART showed benefits for both modalities. However, as IMPT is more conformal, the magnitude of dosimetric changes was more pronounced compared to VMAT. Large anatomic variations had a severe impact on treatment plan quality for both VMAT and IMPT. ART is justified in those cases irrespective of treatment modalities.</p></div

COVID-19 Era Effect on Pandemic and Post-pandemic Pediatric Telemedicine Use: A Survey of the European Academy of Pediatrics Research in Ambulatory Settings Network

Background: During the COVID-19 pandemic, telemedicine use has increased within community pediatrics. This trend runs counter to reluctance to adaptation of the new mode of healthcare that existed prior to the pandemic. Little is known about what we can expect after the pandemic: if physicians will opt for telemedicine modalities and if tele-pediatrics will continue to be a significant mode of community pediatric care. ----- Objective: The goal of this study was to survey primary pediatric care providers as to their experiences and clinical decision making with telemedicine modalities prior to and during the COVID-19 pandemic, as well as their projected use after the pandemic ends. ----- Material and methods: Using the EAPRASnet database we surveyed pediatricians throughout Europe, using a web-based questionnaire. The survey was performed during the COVID-19 pandemic (June-July 2020), assessed telemedicine use for several modalities, prior to and during the pandemic as well as predicted use after the pandemic will have resolved. Participants were also surveyed regarding clinical decision making in two hypothetical clinical scenarios managed by telemedicine. ----- Results: A total of 710 physicians participated, 76% were pediatricians. The percentage of respondents who reported daily use for at least 50% of all encounters via telemedicine modalities increased during the pandemic: phone calls (4% prior to the pandemic to 52% during the pandemic), emails (2-9%), text messages (1-6%), social media (3-11%), cell-phone pictures/video (1-9%), and video conferencing (1-7%) (p < 0.005). The predicted post-pandemic use of these modalities partially declined to 19, 4, 3, 6, 9, and 4%, respectively (p < 0.005), yet demonstrating a prospectively sustained use of pictures/videos after the pandemic. Reported high likelihood of remotely treating suspected pneumonia and acute otitis media with antibiotics decreased from 8 to 16% during the pandemic to an assumed 2 and 4% after the pandemic, respectively (p < 0.005). -----Conclusions: This study demonstrates an increased utilization of telemedicine by pediatric providers during the COVID-19 pandemic, as well as a partially sustained effect that will promote telemedicine use as part of a hybrid care provision after the pandemic will have resolved