Impact of baseline and interim quantitative PET parameters on outcomes of classical Hodgkin Lymphoma.

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.

Consolidative mediastinal radiotherapy for advanced-stage classical Hodgkin lymphoma with bulky disease in patients who achieve complete response after chemotherapy in PET-CT era.

Background: The role of consolidation mediastinal radiotherapy (RT) for mediastinal bulky disease in advanced-stage classical Hodgkin lymphoma (cHL) is controversial in the positron emission tomography/computed tomography (PET-CT) era. Materials and methods: We reviewed the medical charts of patients with advanced-stage (clinical stage IIX-IVX) cHL and mediastinal bulky that achieved a complete response after first line chemotherapy treatment between August 2010 and December 2020 and compared the results of those who received with those who did not receive consolidation mediastinal RT. Inclusion criteria required PET-CT imaging for staging and response assessment. Results: We included 115 patients; 91 received mediastinal RT and 24 did not. Patient's characteristics were balanced between the two groups. The median age in patients that received and did not receive mediastinal RT was 28 years and 24.5 years, respectively. Median International Prognostic Score among patients that received and did not receive mediastinal RT was 2 and 2.5, respectively. Disease free survival (DFS) was statistically better in patients that received mediastinal RT (p = 0.013). Two-year DFS for patients that received and did not receive mediastinal RT was 95.2% [95% confidence interval (95% CI): 87.6-98.2%] and 76.4% (95% CI: 52.2-89.4%), respectively. Overall survival (OS) was not different between the two groups (p = 0.617). In multivariate analysis, not receiving mediastinal radiotherapy and only achieving partial response (vs. complete response) after 2 cycles of chemotherapy were factors predictive of lower DFS. Conclusion: DFS, but not OS, was superior in patients that received mediastinal RT.

High Dose Chemotherapy With Autologous Stem Cell Transplant for Patients With Advanced Germ Cell Tumors: Real-World Evidence From a Tertiary Cancer Center in Brazil.

BACKGROUND: High-dose chemotherapy followed by stem cell transplant (HDCT) is potentially curative for patients with refractory germ cell tumors (rGCT). There is scarce real-world data supporting its implementation in low- and middle-income countries. We described the experience of our tertiary cancer center in Sao Paulo, Brazil. METHODS: We identified male patients ≥18 years-old with rGCT referred to HDCT after board discussion. Clinical data, including delays in HDCT protocol, were extracted from medical records, and survival outcomes were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazard were used to determine effects on overall survival (OS). RESULTS: From January 2013 to January 2023, 34 patients were referred and considered eligible to receive 2 cycles of HDCT. Most patients had primary testicular tumors (82%), nonseminomatous histology (88%), and poor International Germ Cell Collaborative Group (IGCCCG) (79%). Twenty-three patients received HDCT (1 cycle, n = 8; 2 cycles, n = 15). Main reasons for not receiving any HDCT were death due to progressive disease (n = 1), performance deterioration (n = 7), and failure of stem cell mobilization (n = 3). OS at 2 years was 36.7% for the eligible population, 56.1% for patients who underwent at least 1 HDCT, and 77.1% for those who had ≥2 cycles. The 2-year OS rate for patients not given HDCT was 0%. All patients had delays in protocol, and poor-risk patients had longer intervals from referral to protocol initiation (0.7 vs. 1.8 month, P < .01). CONCLUSION: Outcomes of patients who received ≥1 HDCT were encouraging; however, only 15 from 34 eligible patients were able to receive the planned 2 cycles of HDCT. Further strategies to minimize treatment delays in low- and middle-income countries are needed.

Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma.

AIMS: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. METHODS AND RESULTS: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking <41 packs/year, N0 tambour stage, squamous carcinoma, CD4(+) > 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. CONCLUSION: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.

Postsurgical pyoderma gangrenosum after an autologous stem cell transplantation for multiple myeloma.

We report a man who underwent autologous stem cell transplantation (ASCT) for multiple myeloma. Two months after ASCT, he presented with necrotising cholecystitis due to gallbladder stones and was submitted to laparoscopic cholecystectomy. About a week later, he developed progressive skin ulcers at sites where trochanters had been inserted. Progressive enlargement and necrotic aspect of these ulcers took place despite debridement and large spectrum antibiotics. New ulcers developed at the site of enoxaparin injection at the right arm (pathergy phenomenon). A skin biopsy and clinical evaluation favoured the diagnosis of pyoderma gangrenosum (PG). He was treated with daily methylprednisolone and dapsone with improvement of the lesions. This is the first case in the literature of PG after ASCT. Despite the risk factors, the onset of an autoinflammatory disease right after the transplant is intriguing since PG is extremely rare in immunocompromised patients.

Aumento na expressão de telomerase por fibroblastos ocorre precocemente à expressão de alfa-actina de músculo liso por miofibroblastos no processo de remodelamento da pneumonia intersticial usual / Increased telomerase expression in fibroblasts occurs earlier than myofibroblast alfa-smooth muscle actin expression in the remodeling process of usual interstitial pneumonia

Objetivo: Identificar potenciais marcadores associados à expressão de telomerase em fibroblastos e de α-actina de músculo liso (α-AMS) em miofibroblastos de pulmões de pacientes com fibrose pulmonar idiopática/pneumonia intersticial usual (FPI/PIU). Métodos: Utilizamos cortes histológicos de 34 biópsias cirúrgicas de pulmão de pacientes com FPI, caracterizados, à histopatologia, pelo padrão de PIU. As expressões de telomerase por fibroblastos, de α-AMS por miofibroblastos e tecidual deinterleucina-4 (IL-4), de fator de crescimento transformador-β (TGF- β) e de fator de crescimento de fibroblastos básico (bFGF) foram avaliados por imunohistoquímica e quantificadas pela técnica de contagem de pontos nas áreas pulmonares de colapso (COL),de fibrose mural (FM) e de faveolamento (FV). Resultados: Aexpressão de telomerase foi significativamente maior nas áreasde COL que nas áreas de FM e FV. O mesmo foi observado para a expressão de bFGF. Interleucina-4 e α-AMS tiveram expressão significativamente maior nas áreas de FM. A expressão de TGF-β foi maior nas áreas de COL e FV. Observamos uma associação positiva entre expressão de telomerase e bFGF nas áreas COL, FM e FV. O mesmo ocorreu com a expressão de α-AMS e IL-4. Nas áreas de FM, houve uma correlação negativa entre IL-4e bFGF, e TGF-β apresentou tendência a associação positiva com α-AMS. Análise multivariada revelou que a expressão de IL-4 e α-AMS nas áreas de FM são indicadores independentes de menor sobrevida em modelo estatístico significante incluindo idade, tabagismoe FVC (capacidade vital forçada). Pacientes com expressão de IL-4 menor que 13,5% nas áreas de FMapresentaram melhor sobrevida. O mesmo foi observado para expressão de α-AMS menor que 8,5%. Conclusão: Fibroblastos, com capacidade multiplicativa caracterizada pela expressão de telomerase e de bFGF tecidual, tendem a predominar no estágio precoce de remodelamento da FPI/PIU...

Objective: To identify potential markers associated with fibroblast telomerase and interstitial myfibroblast alpha-smooth muscle actin (α-AMS) expression in patients with idiopathic pulmonary fibrosis/usual intersticial pneumonia (IPF/UIP). Methods:Pulmonary specimens included 34 surgical lung biopsies, histologicallyclassified as UIP, from patients clinically diagnosed with IPF. Fibroblast telomerase expression, interstitial myofibroblast α-AMSexpression and IL-4 (interleukin 4), TGF-β (transforming growth factor beta) and bFGF (basic fibroblast growth factor) tissue expressionwere evaluated by immunohistochemistry and quantifiedin collapsed (COL), mural fibrosis (MF) and honeycombing areas (HC). Results: Telomerase expression was significantly higher in COL areas than in MF and HC areas. The same was observed for b-FGF. Interleukin-4 and α-AMS expression were significantly higher in MF areas. TGF-β expression ws higher in COL and HC areas. We observed a positive correlation between telomerase and bFGF expression in COL, MF and HC areas. The same was noted for α-AMS and IL-4. In MF areas, a negative correlation between IL-4 and b-FGF was obtained and TGF-β tended to positively correlate with α-AMS. In multivariate analysis, IL-4 tissue andα-AMS myofibroblast expression in MF areas were independently predictive of mortality in a statistically significant model including age, tobacco use and FVC (full vital capacity). Patients with IL-4 expression lower than 13.5% in MF areas had better survival. The same was noted for α-AMS expression lower than 8.5%. Conclusion: Fibroblast multiplicative capacity, characterized by telomerase expression and associated with bFGF tissue expression, seems to predominate in the early remodeling process of IPF/UIP, whereas myofibroblast differentiation, characterized by alpha-smooth muscleactin expression and associated with IL-4 tissue expression, seems to lead to the later fibrotic response...