Durable complete remission with local therapies after neoadjuvant and adjuvant nivolumab in recurrent/metastatic head and neck cancer.

Up to 10-15% of patients with first-line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) present with platinum-refractory disease. The anti-PD1 nivolumab is the first therapeutic option in this setting achieving a 19.2% objective response rate and a 7.7-month median overall survival (OS). Given the poor prognosis of platinum-refractory patients, those showing slow progressive disease with no functional status deterioration should maintain nivolumab beyond progression in the absence of severe or unmanageable toxicities. Another strategy is to use local therapies such as radiotherapy and surgical tumor resection in cases of oligometastatic or oligoprogressive disease. Both strategies may significantly improve disease control and OS in these populations. We present the case of a patient with platinum-refractory disease treated with first-line nivolumab beyond progression who achieved a durable complete response after palliative radiation and surgical resection of five tumor lesions. To our knowledge, this is the first reported case of an R/M HNSCC treated with such a strategy outside a clinical trial and contributes to the evidence for combining anti-PD1 agents and local therapies in selected patients with R/M HNSCC.

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer.

BACKGROUND: There are still few data on the activity and safety of cetuximab-based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN). MATERIALS AND METHODS: This was a retrospective study of patients with SCCHN who received cetuximab-based SCAI after programmed cell death protein 1 or programmed cell death ligand 1(PD[L]1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression-free survival (PFS), overall survival (OS), treatment compliance, and toxicity were evaluated. RESULTS: Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximab-based combinations (3-weekly cisplatin-5FU-cetuximab [n = 2], weekly paclitaxel-cetuximab [n = 17], weekly cisplatin-cetuximab [n = 2], weekly carboplatin-paclitaxel-cetuximab [n = 2]). ORR was 56.5% (11 partial response, 2 complete response). DCR was 78.3%. Among 13 objective responders, median best PCTL was -53.5% (range, -30% to -100%). Median OS and PFS were 12 months and 6 months, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, whereas ORR to SCAI achieved 60%. In LCBI-treated patients, median PFS with LCBI was 8 months and median PFS and OS with SCAI were 7 months and 12 months, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 adverse events (AEs) occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment-related deaths. CONCLUSION: Cetuximab-based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era. IMPLICATIONS FOR PRACTICE: Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) after progression to PD-1/PD-L1 inhibitors. Objective response rate was higher than and progression-free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, well-tolerated regimens. These observations have implications for current practice because of the limited evidence to date in SCCHN and the scant therapeutic options in this disease and invite to elucidate which may be the best treatment sequence for patients with head and neck cancer in the IO era.

Toxocariasis affecting brain stem and skull base.

BACKGROUND: Toxocariasis is a helminthic infection caused by a nematode that mainly affects populations in tropical and subtropical latitudes. Humans are potential paratenic hosts, and clinical disease occurs as a result of parasite migration through intestinal tissue. We present a clinical case of otorhinolaryngological affectation by Toxocara canis. CASE PRESENTATION: A 60-year-old male from Ecuador, resident in Spain for 5 years, evaluated in the emergency department for presenting headache, otorrhea and left ear pain. Computed tomography (CT) and magnetic resonance imaging (MRI) reported a large mass of the nasopharynx with infiltration of the skull base, intracranial extension and a lesion in the left pons without being able to exclude metastases. Two Functional Endoscopic Sinus Surgery (FESS) biopsies were negative for malignancy. Despite not meeting the diagnostic criteria established by the existing literature, the clinical and radiological presentation, the presence of risk factors, a positive serology for Toxocara canis (IgGELISA) and the absence of alternative diagnosis were considered sufficient criteria to establish toxocariasis with inflammatory lesions in the nasopharynx and pons as the most probable diagnosis. Treatment with albendazole (400 mg / 12 h) and corticosteroids (1 mg / kg for 5 days) was started and continued for one month. Post treatment negative serology, and MRI and CT post treatment controls were performed after one year, both showing a decrease in lesion of the clivus as well as the pons. CONCLUSIONS: With the appropriate personal history, toxocariasis should be included in the differential diagnosis of infiltrating lesions of the skull base with a negative study of tumor histology. Albendazole treatment has been shown to control and cure the disease.

Nasoethmoidal Intestinal-Type Adenocarcinoma Treated with Cetuximab: Role of Liquid Biopsy and BEAMing in Predicting Response to Anti-Epidermal Growth Factor Receptor Therapy.

Sinonasal intestinal-type adenocarcinomas (SNS-ITAC) are very rare tumors that resemble colorectal cancer in many of their pathological and molecular characteristics. Indeed, in most published series, 10%-14% of SNS-ITAC harbor mutations in KRAS. There is no standard systemic treatment in recurrent or metastatic SNS-ITAC, and there is no evidence of the use of any targeted agent in this entity. We present the case of a recurrent nasoethmoidal ITAC informed as RAS and BRAF wild-type by standard real-time polymerase chain reaction methods and treated with first-line cetuximab and irinotecan without response. Circulating tumor cells coupled to highly sensitive DNA analyses unveiled a mutation in KRAS exon 2 codon 12. Subsequent studies in the primary tumor using BEAMing detected a mutation in the same codon, confirming the KRAS mutated status of the tumor, and possibly explaining the absence of treatment response. This case exemplifies how liquid biopsy can aid in the correct and real-time molecular characterization of tumors even in a rare nonmetastatic cancer of the head and neck. KEY POINTS: Sinonasal intestinal type adenocarcinomas (SNS-ITAC) are rare tumors that commonly develop after a prolonged exposure to organic dusts (wood, leather, etc.), and that resemble colorectal cancer in some of their morphological and molecular characteristics.KRAS mutations have been described in 10%-14% in most series. However, its predictive value for guiding treatment decisions with targeted therapies (i.e., anti-epidermal growth factor receptor [EGFR] therapy) has not been defined.The first case of an SNS-ITAC treated with anti-EGFR therapy (cetuximab) is reported. Analysis of DNA from circulating tumor cells (CTCs) unveiled a mutation in KRAS not detected by standard methods in the primary tumor. However, RAS analysis using BEAMing detected a mutation in the primary tumor in the same codon of KRAS originally detected in CTCs, altogether possibly explaining the lack of treatment response.Liquid biopsy may allow for an accurate molecular diagnosis in rare, organ-confined tumors where few therapeutic options exist. Highly sensitive molecular diagnostics may aid in better characterizing rare entities harboring potentially druggable targets.

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer.

Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fluoropyrimide-ineligible patients with recurrent or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2, 80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients [all grade 3 (anemia, neutropenia, thrombopenia, hypertension)]. The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN.

Major pathological response and durable locoregional control after neoadjuvant pembrolizumab-carboplatin-paclitaxel in head and neck cancer.

Head and neck cancers are increasingly being diagnosed in elderly patients, where standard curative-intent, therapeutic options are often too aggressive for frail, malnourished and heavily comorbid patients. Since the incorporation of immune checkpoint inhibitors (ICIs) a few small studies have reported promising safety and efficacy with ICIs in the neoadjuvant locally-advaced setting. We present the case of an elderly, frail and comorbid patient, with a high-PDL1 expressing and very locally-advanced unresectable oral cavity cancer, that was treated with the combination of pembrolizumab and weekly carboplatin and paclitaxel, achieving a major pathological response, that permitted to de-escalate adjuvant therapy after surgery and is free of locoregional relapse 7 months after surgery. This is, to our knowledge, the first patient treated with neoadjuvant chemo-immunotherapy outside a clinical trial in SCCHN.

Single-session treatment of benign thyroid nodules with radiofrequency ablation: Results at 6 months in 24 patients. / Resultados de una sesión única de ablación por radiofrecuencia en nódulos tiroideos benignos: Resultados a 6 meses en 24 pacientes.

OBJECTIVE: To evaluate the efficacy and safety of one single-session of radiofrequency ablation (RFA) performed in thyroid benign and predominantly solid nodules. PATIENTS AND METHOD: Unicentric retrospective study in usual clinical setting that included patients with solid and benign thyroid nodules treated with one single session of RFA and with folllow-up of at at least 6 months after the procedure. RFA was performed as an alternative to surgery in cases of pressure symptoms or nodular growth evidence. Patients were evaluated basally and at one, 3 and 6 months after RFA and also at 12 months if the follow-up was available. In each evaluation efficacy variables were recorded (percentual change from basal volume, percentage of nodules reaching a volume reduction above 50% from baseline, patients with disappearance of pressure symptoms and the possibility of antithyroid drug withdrawal) and safety variables were also registered including minor complications (pain needing analgesic drugs, hematoma) and major complications (voice changes, braquial plexus injury, nodule rupture and thyroid dysfunction). RESULTS: Twenty-four patients with a follow-up of at least 6 months after RFA were included, 16 of them with more than 12 months of follow-up. Mean nodule volume changed from 25.4±15.5ml basally to 10.7±9.9ml at month 6 (P<.05) and to 9.9±10,4ml at month 12 in 16 nodules. Six months after RFA mean volumetric reduction was 57.5±24% and 65% of the nodules reached a volume reduction above 50% from baseline. Median percentage of reduction at month 6 was 50.4±25.8% for nodules with a basal volume above 20ml (n=13) and 65.3±20.1% for nodules with a lower basal volume (n=11). Pressure symptoms reported in 12 patients disappeared in all cases. Antithyroid drugs could be stopped in 3 of 4 cases treated before RFA. A mild and transient pain responsive to conventional analgesic drugs was recorded in 9 patients during the 24h after the procedure and in 7 a small perithyroid and transient hematoma was observed in the 48 following hours. One major complication was described as a nodule rupture that recovered spontaneously. There were no changes in hormonal values in euthyroid cases. CONCLUSION: A single session of RFA seems to be an effective and safe procedure in patients with solid thyroid nodules with pressure symptoms or relevant growth evidence. As an outpatient and scarless procedure with no need of general anaesthesia it could become an useful alternative to lobectomy when surgery is refused or in patients at high surgical risk.

Correlation Between Optical Coherence Tomography and Magnetic Resonance Imaging of Rectus Muscle Thickness Measurements in Graves' Ophthalmopathy.

PURPOSE: To assess the correlation between optical coherence tomography (OCT) and magnetic resonance imaging (MRI) measurements of extraocular rectus muscle thickness in patients with Graves' ophthalmopathy. METHODS: This was a cross-sectional observational study conducted in 62 eyes of 31 patients with Graves' ophthalmopathy. The disease phase was inactive in 20 patients and active in the remaining 11. The OCT measurements obtained were: medial rectus thickness at 7.2 and 9.2 mm from the limbus and lateral rectus thickness at 8.5 mm from the limbus. MRI measurements were maximum transversal diameter (T-MRI), craniocaudal diameter (CC-MRI), and muscle area (A-MRI). RESULTS: For the whole patient cohort, correlation emerged between the OCT-MR and T-MRI measurements (R = 0.428 to 0.576; P ≤ .002), A-MRI (R = 0.562 to 0.674; P < .001), and CC-MRI (R = 0.286 to 0.293; P ≤ .046). In patients with clinically active Graves' ophthalmopathy, correlations with T-MRI (R = 0.576 to 0.604; P ≤ .010) and A-MRI (R = 0.678 to 0.706; P < .001) were higher. No correlations were detected between OCT and MRI measurements of lateral rectus thickness (P ≥ .177), regardless of disease phase. CONCLUSIONS: The correlations observed suggest OCT could be a complementary assessment or screening method to detect thickening of the anterior portion of the medial rectus muscle in patients with Graves' ophthalmopathy, which may be especially useful when MRI is not available. [J Pediatr Ophthalmol Strabismus. 2019;56(5):319-326.].

Resultados de una sesión única de ablación por radiofrecuencia en nódulos tiroideos benignos: Resultados a 6 meses en 24 pacientes / Single-session treatment of benign thyroid nodules with radiofrequency ablation: Results at 6 months in 24 patient

Objetivo: Valorar la eficacia y la seguridad de una sesión única de ablación por radiofrecuencia (ARF) en pacientes con nódulos tiroideos benignos y de predominio sólido. Pacientes y método: Estudio unicéntrico retrospectivo de práctica clínica habitual en el que se incluyeron pacientes con nódulos tiroideos sólidos benignos sometidos a una sesión única de ARF con seguimiento de al menos 6 meses tras procedimiento, indicada como alternativa a la cirugía por presentar clínica local compresiva y/o evidencia de crecimiento nodular. Los pacientes fueron evaluados antes, al mes, 3 meses y 6 meses de la ARF, así como a los 12 meses en aquellos con seguimiento disponible. En cada evaluación se recogieron variables de eficacia (cambio porcentual del volumen nodular, el porcentaje de nódulos con reducción volumétrica mayor del 50% respecto al volumen inicial, la desaparición de los síntomas de compresión y la posibilidad de retirar la medicación antitiroidea en aquellos casos bajo tratamiento) y variables de seguridad, incluyendo complicaciones menores (dolor que precisó de analgesia convencional, hematoma peritiroideo de reabsorción espontánea) y complicaciones mayores (cambios en la voz, daños en el plexo cervical, ruptura nodular, disfunción tiroidea). Resultados: Se describen los resultados en 24 pacientes con seguimiento de hasta 12 meses en 16 de ellos. El volumen nodular medio pasó de 25,4 ± 15,5 ml antes de la ARF a 10,7 ± 9,9 ml a los 6 meses (p < 0,05) y a 9,9 ± 10,4 ml a los 12 meses (en 16 casos evaluados), resultando la reducción porcentual de volumen significativa desde el mes siguiente al procedimiento. A los 6 meses la reducción media alcanzada fue del 57,5 ± 24% y el 65% de los nódulos presentaban una reducción de volumen mayor del 50%. En aquellos nódulos con un volumen inicial mayor de 20ml (n = 13) la reducción porcentual a los 6 meses fue del 50,4 ± 25,8% frente al 65,3 ± 20,1% en los nódulos de menor volumen inicial (n = 11). La sintomatología compresiva desapareció desde el primer mes en los 12 pacientes que la referían. La medicación antitiroidea pautada antes de la ARF en 4 casos pudo ser retirada en 3. En 9 pacientes se registró la presencia de dolor leve transitorio en las primeras 24 h, que respondió a analgésicos convencionales, y en 7 se objetivó un pequeño hematoma peritiroideo de reabsorción espontánea en la ecografía de control a las 24 a 48 h de la ablación. Al mes de la ARF se observó un caso de rotura nodular, que se resolvió de manera espontánea. No se apreciaron cambios en los valores hormonales en los pacientes eutiroideos. Conclusión: Una sesión única de ARF parece un tratamiento eficaz y seguro en pacientes portadores de nódulos tiroideos benignos sólidos y con clínica compresiva y/o evidencia de crecimiento nodular relevante. Al ser un procedimiento ambulatorio que no precisa anestesia general ni incisión cutánea podría convertirse en una alternativa útil a la cirugía en los casos en que esta sea rechazada o se considere de alto riesgo

Objective: To evaluate the efficacy and safety of one single-session of radiofrequency ablation (RFA) performed in thyroid benign and predominantly solid nodules. Patients and method: Unicentric retrospective study in usual clinical setting that included patients with solid and benign thyroid nodules treated with one single session of RFA and with folllow-up of at at least 6 months after the procedure. RFA was performed as an alternative to surgery in cases of pressure symptoms or nodular growth evidence. Patients were evaluated basally and at one, 3 and 6 months after RFA and also at 12 months if the follow-up was available. In each evaluation efficacy variables were recorded (percentual change from basal volume, percentage of nodules reaching a volume reduction above 50% from baseline, patients with disappearance of pressure symptoms and the possibility of antithyroid drug withdrawal) and safety variables were also registered including minor complications (pain needing analgesic drugs, hematoma) and major complications (voice changes, braquial plexus injury, nodule rupture and thyroid dysfunction). Results: Twenty-four patients with a follow-up of at least 6 months after RFA were included, 16 of them with more than 12 months of follow-up. Mean nodule volume changed from 25.4 ± 15.5 ml basally to 10.7 ± 9.9 ml at month 6 (P < .05) and to 9.9 ± 10,4 ml at month 12 in 16 nodules. Six months after RFA mean volumetric reduction was 57.5 ± 24% and 65% of the nodules reached a volume reduction above 50% from baseline. Median percentage of reduction at month 6 was 50.4 ± 25.8% for nodules with a basal volume above 20 ml (n = 13) and 65.3 ± 20.1% for nodules with a lower basal volume (n = 11). Pressure symptoms reported in 12 patients disappeared in all cases. Antithyroid drugs could be stopped in 3 of 4 cases treated before RFA. A mild and transient pain responsive to conventional analgesic drugs was recorded in 9 patients during the 24 h after the procedure and in 7 a small perithyroid and transient hematoma was observed in the 48 following hours. One major complication was described as a nodule rupture that recovered spontaneously. There were no changes in hormonal values in euthyroid cases. Conclusion: A single session of RFA seems to be an effective and safe procedure in patients with solid thyroid nodules with pressure symptoms or relevant growth evidence. As an outpatient and scarless procedure with no need of general anaesthesia it could become an useful alternative to lobectomy when surgery is refused or in patients at high surgical risk