Squamous Cell Carcinoma Of Base Research Articles

Abstract CT107: Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi-NT in Patients with Advanced Solid Tumors

Abstract BACKGROUND: Intra-tumoral Clostridium novyi-NT (non-toxic) is an attenuated strain of C. novyi lacking alpha toxin replication within hypoxic tumor regions, causing tumor cell lysis and inflammation. Immunotherapy (IO) augments anticancer activity with intratumoral agents in prior preclinical and clinical studies. This phase 1b dose escalation study assessed safety and potential synergistic effects of pembrolizumab and C. novyi-NT in advanced solid tumors. METHODS: We enrolled patients with percutaneous injectable, solid tumors to receive single intratumoral injection of C. novyi-NT administered on Day 8 across 4 dose cohorts (3 × 10^4 to 100 × 10^4 spores, 3+3 design) with pembrolizumab 200mg IV Q3weekly starting on Day 0 up to 24 months. Primary objectives: Safety, tolerability and maximum tolerated dose (MTD) of combination. Secondary objectives: anti-tumor activity of combination in the injected tumor lesion and overall response by iRECIST 1.1. RESULTS: At data cutoff on October 24, 2022, 16 patients were enrolled and evaluable for toxicity and efficacy. It was well tolerated across all cohorts without dose limiting toxicities with median number of 5 cycles administered (1-34). 10 patients (63%) experienced progression; 1 withdrew consent; 1 completed therapy; 1 came off trial due to toxicity (immune related dermatitis) and 3 patients remain on trial. Median age was 62.5 years (40-71) while all patients (100%) had performance status of 1. 8 (50%) received prior IO and 7 (44%) had > 4 lines of prior therapies. Confirmed overall objective response rate (ORR) was 25% in 4 patients [non-keratinizing undifferentiated nasopharyngeal squamous carcinoma (NPC), human papilloma virus positive squamous cell carcinoma of base of tongue, vulvar melanoma and chordoma] with 3 partial responses (PR) and 1 complete response (CR). Among responders, median duration of response was 8.18 months and 1/4 (25%) had prior IO. NPC patient completed 24 months on trial to completion with best response at PR (-87%) while vulvar melanoma patient remains on trial with best response at CR (-100%). Median injected tumor size was 2.65cm (1-11) with confirmed ORR in injected lesions at 19% with 2 PRs and 1 CR. Most prevalent grade 1 and 2 adverse events were injection site reaction (25%), pyrexia (19%), pruritus (13%), leukopenia (13%) and anemia (13%). No grade 3 or 4 treatment related adverse events noted. Signs and symptoms of C. novyi-NT germination (infection) including fever, injection site pain, erythema, swelling, tenderness, and in some cases, ulceration, spontaneous drainage, tissue sloughing, bleeding, and malodor were observed in 5 patients. CONCLUSIONS: Intratumoral C. novyi-NT with pembrolizumab demonstrates clinical activity with favorable tolerability in patients regardless of tumor histology. This study is ongoing to define the recommended phase 2 dose (NCT03435952). Citation Format: Blessie Elizabeth Nelson, Filip Janku, Siqing Fu, Ecaterina I. Dumbrava, David S. Hong, Daniel Karp, Aung Naing, Jordi Rodon, Apostolia Tsimberidou, Rodabe N. Amaria, Anthony Conley, Senthil Damodaran, Kanwal P. Raghav, Brent L. Kreider, David Tung, Mary Varterasian, Khashayarsha Khazaie, Sarina Piha-Paul. Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi-NT in Patients with Advanced Solid Tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT107.

Response to R-CHOP in HPV-related squamous cell carcinoma of base of tongue: a case report

BackgroundSynchronous squamous cell carcinoma of the head and neck (HNSCC) and non-Hodgkin’s lymphoma is a rare clinical scenario. It is unknown whether the R-CHOP chemotherapy for lymphoma would also be active against HNSCC. Herein, we present such a case and a review of the literature.Case presentationA 64 year-old female presented with painless jaundice. CT demonstrated a retroperitoneal mass and pathology showed follicular lymphoma. A base-of-tongue HPV+ squamous cell carcinoma was found incidentally on staging CT. R-CHOP chemotherapy was initiated. After 3 cycles of R-CHOP the lymphoma had a complete metabolic response and, unexpectedly, the HNSCC also demonstrated excellent response. The patient received another 3 cycles followed by radiation to the HNSCC and to date is in remission for both cancers.ConclusionsThis case highlights the exquisite sensitivity of HPV-related HNSCC, which should be taken into consideration in treatment prioritization of a concurrent diagnosis of a second cancer.

Abstract C14: Type of insurance affects risk of late-stage oral and pharyngeal cancer diagnosis

Abstract Differences in stage of diagnosis for oral and pharyngeal cancer OPC based on race, ethnicity, and socioeconomic status have been documented with poor and Blacks having the poorest outcomes. To understand points of intervention, we examined how stage at diagnosis is influenced by gender, race, ethnicity, 3rd party payer, and marital status separately for oral sites and pharyngeal sites. Oral sites include squamous cell carcinomas of tongue, floor of mouth, and palate; Pharyngeal sites include squamous cell carcinomas of base of tongue, tonsil, hypopharynx, and oropharynx. Our rationale for separating these sites is the dramatic difference in stage of diagnosis between oral and pharyngeal (1). In this analysis, we add a modeling component to our previous work and focus on the effect of insurance on stage of diagnosis. Methods: OPC cancer patients diagnosed between 2000 and 2008 were examined using data from the Florida Cancer Data System. A total of 12938 patients with OPC cancers were identified, with 4531 oral cavity cases and 8407 pharynx cases. Overall, 72.2% of patients were male, 92% were white, and 8.5% were Hispanic. The primary outcome variable stage of diagnosis was dichotomized into: localized versus late (regional and distant) stage diagnosis. Two logistic regression models, separated for oral SCC and pharyngeal SCC, were built with predictor variables including gender, race, ethnicity, insurance used, and marital status. Categories of insurance coverage were: 1) No insurance, 2) Private insurance, 3) Medicaid, 4) Medicare, and 5) Other. Age at diagnosis and year of diagnosis were controlled for the models. Results: Compared to Whites, Blacks were less likely to have private insurance (19.47% versus 30.64% for Whites) but more likely to have no insurance (12.46% versus 7.06% for Whites) and Medicaid coverage (20.74% versus 6.31% for Whites). Compared to Non-Hispanics, Hispanics were more likely to have no insurance (12.49% versus 7.01% for Non-Hispanics) and Medicaid coverage (15.11% versus 6.74% for Non-Hispanics). However, the percentages covered by private insurance were similar for Hispanics (28.87%) and Non-Hispanics (29.83%). The percentage with Medicare coverage were similar across groups ranging from 33%-39%. Insurance Race Ethnicity White Black Non-Hispanic Hispanic No insurance 7.06% 12.46% 7.01% 12.49% Private 30.64% 19.47% 29.83% 28.87% Medicaid 6.31% 20.74% 6.74% 15.11% Medicare 39.9% 33.01% 39.91% 33.48% other 16.09% 14.31% 16.50% 10.05% Based on the regression analysis, having private insurance (OR=0.48, p<0.001; OR=0.66, p=0.004) or Medicare (OR=0.46, p<0.001; OR=0.54, p<0.001) coverage were protective compared to no insurance in having a late-stage diagnosis at either oral or pharyngeal sites. On the other hand, being enrolled in Medicaid was no different than having no insurance in stage of diagnosis for both oral and pharyngeal cancer. Many of the other observed relationships were as expected: being male was a risk factor for late stage dx for both oral and pharyngeal cancer (OR=1.52, p<0.001; OR=1.54, p<0.001) as was being Hispanic (OR=1.27, p=0.021; OR=1.29, p=0.027). Being Black was a risk factor for late stage oral cancer diagnosis (OR=2.00, p<0.001) but not pharyngeal cancer (OR=1.18, p=0.1596). Being married was protective for oral and pharyngeal sites (OR=.74, p<0.001; OR=0.80, p<0.001, respectively). Conclusions: Medicare and private insurance were protective against late stage diagnosis. Benefits associated with Medicaid coverage provide no additional protection for late stage diagnosis compared to having no insurance pointing to a clear need for a review of the diagnostics services available. 1. Guo Y, McGorray SP, Riggs CE, Jr., Logan HL. Racial disparity in oral and pharyngeal cancer in Florida in 1991-2008: mixed trends in stage of diagnosis. Community Dentistry and Oral Epidemiology 2012;72(1):68-74. Citation Format: Henrietta L. Logan. Type of insurance affects risk of late-stage oral and pharyngeal cancer diagnosis. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C14.

English

Traditionally considered to be a loco-regional disease, head neck cancers metastasize infrequently to distant sites. Among these, skin metastases have been rarely reported and almost always they have been encountered during or after treatment of primary. We present here a case of squamous cell carcinoma of base of tongue with multiple dermal metastases at initial presentation. This report signifies that rarity of such cases must not delay the confirmation of diagnosis since these patients already carry a dismal prognosis. only a month back. Other than a history of heavy smoking for the last 30 years, there were no other forms of addiction. He was neither diabetic, nor hypertensive and had a ECOG performance of '2'. Clinical examination and contrast enhanced CT scan of neck revealed irregular hard mass in base of tongue eroding into left retromolar trigone and hard bilateral neck nodes with the largest one measuring 5.4X 6.2cm.A specimen from the tongue mass showed grade 2(moderately differentiated) squamous cell carcinoma with peri-neural invasion but no lympho-vascular tumor emboli was detected. Punch Biopsy from a skin nodule revealed metastatic squamous cell carcinoma deposits. Metastatic work-up revealed no other sites of metastasis. Routine investigations were essentially normal. The disease was staged to be cT4aN3M1. Salvage chemotherapy with Docetaxel (80mg/m2 on day 1), cisplatin (75mg/m2 on day 1) and 5-Flurouracil (1000mg/m2 day1-4) was initiated within a week and he has tolerated well two such cycles so far. A partial response of the primary and neck nodes has been documented and the skin nodules have completely disappeared (figure 2).

Random Synchronous Malignancy in Male Breast: A Case Report

We report here a case of a random synchronous male breast malignancy in a patient with a known base of tongue malignancy that was incidentally detected on a whole body 18-fluorine deoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT). Patient was referred to us for PET/CT staging and radiotherapy planning for a poorly differentiated squamous cell carcinoma of base of tongue. Histopathologically, the incidentally detected breast lesion was proven to be an invasive ductal carcinoma. 18F-FDG PET/CT being a whole body imaging modality is known to detect a considerable number of synchronous primaries. Synchronous malignancies in the head and neck area and the upper aerodigestive tract are well established. However, synchronous malignancy in male breast is reportedly uncommon. Our case is unique for the fact that a random synchronous dual malignancy of base of tongue and breast in a male patient was detected during a whole body 18F-FDG PET/CT imaging.

Carcinoma base of tongue: Single institution 15 year experiences

To report the outcome with radiotherapy and concomitant chemoradiotherapy in patients with locally advanced squamous cell carcinoma base of tongue treated and followed up at single institution over a period of 15 years. This study was carried out by auditing the medical records of 103 patients treated at our institution between 1991 and 2006. Mean age with standard deviation of patients in the Radiotherapy only (group I) and chemoradiotherapy (group II) was 55.26 ± 14.16 and 49.81 ± 12.16 years. 46 patients were treated with radiotherapy alone and 57 patients were treated with concurrent chemo radiotherapy using infusion cisplatinum 3 weekly and 5 fluorouracil twice weekly. Mean follow up was 13.35 months. All the patients characteristic and treatment characteristics were recorded. There were 81 men and 22 women in the study. Group I contains 15 and 31 cases of stage III and IV tumors while group II contains 19 and 38 cases of stage III and IV respectively. Group II has shown improved loco regional control rate for the T3 and T4 tumors as compared to group I. Disease free survival and overall survival in the group II is 25.51 months and 22.53 months while group I has 8.67 months and 6.74 months respectively. Grade III mucosal toxicity incidence was higher in group II as compared to group I. In locally advanced squamous cell carcinoma of base of tongue tumors concomitant chemoradiotherapy with infusional cisplatinum and 5 fluorouracil results in higher disease free and overall survival as compared to radiotherapy as single modality. This better tumor response with chemoradiotherapy comes at cost of higher incidence of mucosal toxicity.

Metastatic Tumors to the Penis

This study presents clinicopathologic and outcome features of 17 patients with metastatic tumor to the penis. Primary sites and histological types were as follows: 6 urothelial carcinomas of urinary bladder, 4 prostatic carcinomas (2 adenocarcinomas and 2 adenosquamous carcinomas), 2 colorectal adenocarcinomas, 2 pulmonary carcinomas (1 squamous cell carcinoma and 1 small cell carcinoma), 1 squamous cell carcinoma of base of the tongue, 1 cutaneous malignant melanoma, and 1 acute myeloid leukemia. Literature review revealed similar distribution of organ sites in 437 cases. Most of our tumors were metachronous. Interval between primary and penile metastasis ranged from 3 to 60 months (mean 16 months). Most of the patients presented with a penile mass. Priapism was observed in 4 patients. The shaft was the commonest anatomical site involved (12 cases). Tumor emboli were usually found in the erectile tissues (14 cases), mainly corpora cavernosa. A total of 14 patients died of disseminated disease. Time interval between primary tumor and penile metastasis ranged from 3 to 60 months (mean 19 months) and between diagnosis of penile metastasis and death ranged from 0.25 to 18 months (mean 6 months), significantly shorter (P = .0058). Patients presented a median survival of 18 months from primary treatment and 5 months after diagnosis of penile metastasis. None of the patients who died of disseminated cancer lived more than 18 months after pathological diagnosis. Clinical evidence of penile involvement in a patient with a known malignancy is an ominous sign and should alert the clinicians to the dismal prognosis.

Squamous cell carcinoma of base of tongue in a patient with Fanconi's anemia treated with radiation therapy: Case report and review of literature

Fanconi's anemia (FA) is a rare autosomal recessive genetic disorder characterized by congenital anomalies, progressive aplastic anemia, and a predisposition for malignancies. Solid tumors in the head and neck region, especially in the tongue, are rarely observed. Management of these patients is a challenge because of hematological complications and increased toxicities. We report a case of Fanconi's anemia in a 27-year-old man with carcinoma of the base of tongue (T2N0M0) who was treated with radical radiation therapy to a dose of 70 Gy/35 fractions/51 days. We have also done in vitro radiosensitivity tests. The patient tolerated the radiation treatment well and completed it without any interruptions. In vitro studies did not show any increased radiosensitivity in this patient. Head and neck cancer in a patient with FA requires individualized treatment. The decision about opting for different modalities should be based on a balanced approach with respect to locoregional control and toxicities of the treatment.

P2.20. Prognostic factors influencing survival of squamous cell carcinoma of base of tongue

P2.20. Prognostic factors influencing survival of squamous cell carcinoma of base of tongue

Paradigma da disseminação linfática no carcinoma espinocelular da base da língua

OBJETIVO: O carcinoma espinocelular CEC da base da língua tem um comportamento agressivo, disseminando-se precocemente para o pescoço uni ou bilateralmente. O objetivo deste trabalho é estabelecer critérios de tratamento eletivo ou terapêutico dos linfonodos cervicais metastáticos ou não para o CEC da base de língua. MÉTODO: Estudo retrospectivo de 290 pacientes com CEC de base de língua atendidos no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital Heliópolis, Hosphel, São Paulo, de 1997 a 2000. Após análise loco-regional, foram classificados segundo os níveis I, II, III, IV e V do estadiamento TNM da UICC (1998). Os resultados foram analisados segundo o teste do Qui-quadrado para o estudo da associação de sítios, tamanho do tumor, presença de metástases e invasão da linha média. RESULTADOS: Houve um predomínio do sexo masculino em relação ao feminino (9:1), da 6ª década, dos fumantes e etilistas (83,8%). Quanto à disseminação linfonodal, diagnosticamos N0 (21,0%), N1 (13,4%), N2 (43,1%), N3 (22,5%) e níveis I(11,6%), II(69,0%), III (13,5%), IV (2,8%) e V (3,1%). Quanto à invasão da linha média, não houve relação significante com o nível comprometido. CONCLUSÃO: O tratamento do CEC da base da língua deve envolver o sítio primário e os níveis de disseminação linfonodal, uni e bilateral.

Squamous cell carcinoma of the base of tongue with initial presentation of cystic metastasis in contralateral cervical lymph node

A case of squamous cell carcinoma of the base of tongue presenting initially as a cystic metastasis in the contralateral neck is described. The patient complained of a painless mass in the left neck, which was removed and histologically diagnosed as cystic malignancy. One year and seven months after the removal, a squamous cell carcinoma of the right tongue base and cystic metastases of the right neck were discovered. The histologic similarity among these three lesions strongly indicated the cystic metastases in the bilateral neck were from the squamous cell carcinoma of the tongue base.

Quality of life following resection, free flap reconstruction and postoperative external beam radiotherapy for squamous cell carcinoma of the base of tongue.

This study was conducted to evaluate quality of life in a cohort of patients with squamous cell carcinoma of the tongue base, treated with primary surgery, reconstruction and postoperative radiotherapy. Twelve patients were assessed in a cross-sectional study using the University of Washington Quality of Life Instrument (UW-QOL). All patients underwent external beam irradiation following primary resection of their tumour and reconstruction. Patients on average reported their overall and health related QOL to be good. Functionally they had good pain control, speech intelligibility, activity and recreational levels. There were some limitations in chewing, swallowing and taste. The results suggest that surgical resection can offer good functional and overall QOL results for advanced tumours when combined with reconstruction. The morbidity associated with postoperative radiotherapy includes reduced swallowing, taste, saliva production and difficulty chewing.

Skin and Eye: Uncommon Sites of Distant Metastasis from Tongue Base Squamous Cell Carcinoma

The frequency of non-lymphatic distant metastases from primary head and neck squamous cell carcinoma (SCC) appears to be higher than previously presumed. The general conditions of the affected patients, who usually also present with locoregional recurrences, are so impaired as to limit the use of available methods for diagnosing the distant spread of head and neck SCC. The incidence reported in autopsy studies is approximately three to four times higher than that in clinical studies. Lung metastases from head and neck SCC are most common, followed by metastases to bone and liver. Metastases to the skin are unusual. Secondary ocular localizations of head and neck SCC are exceedingly rare. We report the first case of synchronous intraocular (involving the choroid and vitreous body) and cutaneous metastases from a recurrent tongue base SCC in a 64-year-old woman who had undergone radiotherapy, bilateral neck dissection and chemotherapy. Cytological evaluation of vitreous aspirate and histological diagnosis of the skin lesion were performed < 1 month before the patient's death. Skin metastases occur in 1–4% of patients with diagnosed head and neck SCC and are usually associated with advanced or recurrent disease. To the best of our knowledge, fewer than 10 cases of ocular metastases from head and neck SCC have been reported. The average survival time after diagnosis of ocular or skin metastases from head and neck SCC is ≈ 7 months. Treatment for eye and skin metastases is palliative and rarely alters patient outcome.

Surgical treatment of squamous cell carcinoma of the base of tongue.

Squamous cell carcinoma (SSC) of the tongue base has historically been shown to be associated with a poor prognosis. We reviewed our experience with primary surgery followed by postoperative radiation therapy (XRT) to determine the impact of our treatment protocols on outcome. We retrospectively reviewed the records of all patients presenting to the University of Pittsburgh with previously untreated SSC of the tongue base between 1980-1997. Patients who were treated nonoperatively were excluded from analysis. Surgical excision of the primary was performed with ipsilateral neck dissection. The contralateral neck was dissected when the primary lesion was located in the midline or for clinically positive contralateral neck nodes. Postoperatively, most patients (93%) received XRT to the primary site and neck. Adjuvant chemotherapy was offered if histologic signs of aggressive behavior were identified (multiple nodes or extracapsular spread). Of 87 patients identified, 39 (45%) were initially seen with T1 or T2 tumors. Seventy-nine patients (91%) were initially seen with stage III or IV disease. Contralateral neck dissection was performed in 36 patients (41%). Metastatic disease was demonstrated in 84% of ipsilateral neck nodes and in 47% of contralateral neck nodes. Occult metastases were found in 61% of clinically N0 necks. Local recurrence occurred in 5 patients, regional recurrence occurred in 12 patients, and distant metastases developed in 22 patients. Overall and disease-specific survival rates at 5 years for all patients were 49% and 56%, respectively. The 5 year disease-specific survival rates for stage I, stage II, stage III, and stage IV disease were 100%, 86%, 62%, and 48%. The 5-year disease-specific survival rate was 88% for T1 lesions, 64% for T2 lesions, 58% for T3 lesions, and 30% for T4 lesions (p <.05, log-rank test). Surgical treatment of SCC of the tongue base is highly effective in achieving local disease control and disease-free survival for early lesions. Because both functional outcome and survival are poor after surgical treatment of advanced lesions, we now offer brachytherapy with XRT or participation in a combined chemoradiation protocol rather than primary surgical therapy to patients with advanced disease. Prospective studies are needed to compare the effect of these organ-preserving therapies with traditional combined surgery and XRT to determine the effect on functional outcome and quality of life.

P-glycoprotein expression in the squamous cell carcinoma of the tongue base.

P-glycoprotein (PGP), which is a product of the multidrug resistance gene (MDR1), is an active transmembrane efflux pump responsible for detoxifying normal cells as well as rendering tumor cells resistant to chemotherapy. It has also been implicated to be expressed by more aggressive cancers. It has not been well described in squamous cell carcinoma of the head and neck. In this investigation, an attempt was made to characterize advanced squamous cell carcinoma of the base of tongue with respect to expression of PGP. Using immunohistochemical techniques two anti-PGP monoclonal antibodies (JSB1 and C494) were used to detect PGP in these lesions, and an attempt was made to correlate levels of PGP staining and various tumor parameters. Usefulness of PGP in predicting survival and time to recurrence was also examined for these advanced lesions. All 33 base of tongue lesions showed staining for PGP with these monoclonal antibodies. This was the first study examining utility of C494 in detecting PGP in squamous cell carcinoma at this site. Increased level of PGP expression was seen in better-differentiated tumors as well as in tumors with diploid DNA. A trend of higher PGP expression and decreased survival emerged. This may represent a true relationship, but inherent heterogeneity of PGP expression within cells cannot be excluded. Both antibodies examined appear to be useful in the investigations of PGP distribution in squamous cell carcinomas of the head and neck sites by immunohistochemical techniques. Prognostic value of the level of PGP expression remains to be seen.