HOLA COVID-19 Study: Evaluating the Impact of Caring for Patients With COVID-19 on Cancer Care Delivery in Latin America.

PURPOSE: The HOLA COVID-19 study sought to evaluate the impact of COVID-19 on oncology practices across Latin America (LATAM), challenges faced by physicians, and how practices and physicians adapted while delivering care to patients with cancer. METHODS: This international cross-sectional study of oncology physicians in LATAM included a 43-item anonymous online survey to evaluate changes and adaptations to clinical practice. Multivariable logistic regression analyses were used to evaluate the association of caring for patients with COVID-19 and changes to clinical practice. RESULTS: A total of 704 oncology physicians from 19 countries completed the survey. Among respondents, the most common specialty was general oncology (34%) and 56% of physicians had cared for patients with COVID-19. The majority of physicians (70%) noted a decrease in the number of new patients evaluated during the COVID-19 pandemic when compared with prepandemic, and 73% reported adopting the use of telemedicine in their practice. More than half (58%) of physicians reported making changes to the treatments that they offered to patients with cancer. In adjusted models, physicians who had cared for patients with COVID-19 had higher odds of changing the type of chemotherapy or treatments that they offered (adjusted odds ratio 1.81; 95% CI, 1.30 to 2.53) and of delaying chemotherapy start (adjusted odds ratio 2.05; 95% CI, 1.49 to 2.81). Physicians identified significant delays in access to radiation and surgical services, diagnostic tests, and supportive care. CONCLUSION: The COVID-19 pandemic has significantly disrupted global cancer care. Although changes to health care delivery are a necessary response to this global crisis, our study highlights the significant disruption and changes to the treatment plans of patients with cancer in LATAM resulting from the COVID-19 health care crisis.

Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma.

NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 µg with five patients included in each dose level except the 900 µg dose (n = 10). Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective response or stable disease) was obtained in 38.46% of patients. Global median overall survival was 20.20 months. Two patients achieved overall survival duration of about 4 and 5 years, respectively. The 900 µg dose resulted in overall survival duration of 19.40 months and was selected as the biological optimal dose.

Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile.

Nimotuzumab is an EGFR-targeting antibody that has demonstrated encouraging clinical results in the absence of severe side-effects observed with other approved anti-EGFR antibodies. We investigated whether different clinical behavior of nimotuzumab is related to its bivalent/monovalent binding profile. Binding properties of nimotuzumab and cetuximab, the most development of anti-EGFR antibodies, were studied in vitro using chip surfaces and cells with varying EGFR expression levels. Experimental observations demonstrated that in contrast to cetuximab, the intrinsic properties of nimotuzumab required bivalent binding for stable attachment to the cellular surface, leading to nimotuzumab selectively binding to cells that express moderate to high EGFR expression levels. At these conditions, both antibodies bound bivalently, and accumulated to similar degrees. When EGFR density is low, nimotuzumab monovalent interaction was transient, whereas cetuximab continued to interact strongly with the receptors. We compared the in vitro anti-tumor efficacy of nimotuzumab and cetuximab. Cetuximab decreased the cell viability and induced apoptosis for all the tested cell lines, effects which did not depend on EGFR expression level. In contrast, nimotuzumab also provoked significant anti-cellular effects, but its anti-tumor capacity decreased together with EGFR expression level. Cetuximab Fab fragment was able to impact tumor cell survival, whereas nimotuzumab fragment totally lost this effect. Tumor-xenograft experiments using cells with a high EGFR expression revealed similar tumor growth inhibiting effects for both antibodies. This study suggests an explanation for nimotuzumab clinical profile, whereby anti-tumor activity is obtained in absence of severe toxicities due to its properties of bivalent binding to EGFR.

Patterns of survival of follicular lymphomas at a single institution through three decades.

Follicular lymphoma (FL) is considered an indolent but incurable disease. It remains to be clarified whether the outcome has changed after the recent introduction of novel treatment modalities. We retrospectively analyzed the outcome of 281 patients with FL treated at the Oncology Institute of Southern Switzerland from 1979 to 2007. Three diagnostic eras were considered, according to the major therapeutic changes: before 1989 ('alkylating agents era', n = 73), 1990 to 1999 ('aggressive regimens and G-CSF era', n = 119), and 2000 to 2007 ('rituximab era', n = 89). The distribution of prognostic factors was similar in the three eras. A significant improvement in cause-specific survival (CSS) was observed over time (p = 0.0088), but not in overall survival. Median CSS was 12.5 years for patients with FL diagnosed before 1989, but was not reached in the more recent groups. The estimated CSS rate at 5 years in the three eras was 80%, 86%, and 91%, respectively. The CSS of patients with FL treated at our institution has improved over the last 25 years. This improvement, already evident before the wide introduction of rituximab in clinical practice, may be a result of the sequential application of effective therapies and improved supportive care.

Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: results of a Phase Ib/IIa study.

NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues. A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant. Twenty two patients were included, twelve at dose level of 200 microg and 10 at 400 microg. The first five doses were administered every other week and then monthly until 9 doses. 12 patients received additional immunizations. Vaccination induced specific anti-NeuGcGM3 IgM, IgG and IgA antibodies responses. Titers of IgM were greater for the highest vaccine doses. Vaccination also elicited DTH response in 45.5% of patients in the lower doses and 77.8% in the higher doses. Toxicities were mostly grade 1 or 2, according CTC-NCI criteria. Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes. Survival analysis was not the goal of this Phase I trial; nevertheless, the fact that seven patients are alive for more than 2 years after inclusion is noteworthy. Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. The prognostic value of autoimmunity and the possibilities of dissociating anti-tumor immunity from autoimmunity deserve further research.

Low prevalence of Chlamydia psittaci in ocular adnexal lymphomas from Cuban patients.

Most ocular adnexal lymphomas (OAL) are extranodal marginal zone B-cell lymphomas (EMZL) of mucosa-associated lymphoid tissue (MALT)-type. Chronic antigen stimulation has been suggested to have a pathogenetic role in EMZL and Chlamydia psittaci chronic infection has been recently associated with the development of OAL in a series of patients from Italy. To assess this association, an evaluation of the presence of C. psittaci was made in a different OAL population. DNA samples were obtained from formalin-fixed, paraffin-embedded sections samples of 26 patients with OAL, 20 non-OAL and 20 benign ocular lesions, diagnosed and treated between 1998 and 2003 at National Institute of Oncology in Havana, Cuba. All samples were histologically reviewed by an expert pathologist. Fluorescence in situ hybrization (FISH) analysis of translocations involving MALT1 was performed. The presence of bacterial DNA was assessed with a multiplex touchdown enzyme time release polymerase chain reaction. DNA sequencing was performed to confirm suspicious bands. Seventy-three percent of the OAL cases were EMZL and 81% were in stage IE. FISH analysis was performed in 13 OAL cases and none of them evidenced MALT1 translocations. DNA of C. psittaci was detected in 11% of the 46 lymphomas: two orbital EMZL and three non-OAL. All 20 benign ocular lesions were negative for C. psittaci. The low prevalence of C. psittaci in OAL suggests geographical differences in the etiology of this entity. International studies are needed to clarify the role of C. psittaci in OALs.