Oropharyngeal Squamous Cell Cancer Research Articles

Prognostic nutritional index (PNI) correlates with survival in head and neck cancer patients more precisely than other nutritional markers - real world data.

The survival benefit with higher body mass index (BMI) of patients suffering from head and neck squamous cell carcinoma (HNSCC) is documented as BMI paradox. As the early re-nourishment of high-risk patients determine survival, we searched for a nutritional status marker suitable for everyday screening. Grouping patients based on the 8th Edition of TNM Classification, we investigated for the first time the candidate nutritional status markers among TNM8 subgroups, including the newly introduced p16 positive oropharyngeal squamous cell cancer (OPSCC) patients. We conducted a retrospective cohort study enrolling 661 patients and collecting anthropometric indices, laboratory parameters, clinical scores, nutritional risk scores. To discover the best one for screening survival analyses and correlation tests were executed. By performing univariate Cox regression, we found three nutritional markers significantly correlating with overall survival (OS) and cancer specific survival (CSS): BMI at diagnosis, percent of weight loss over six months and prognostic nutritional index (PNI). The latter proved to be independent of tumor stage. p16 negative OPSCC patient's OS and CSS did not correlate with BMI, but it did correlate with PNI and percent of weight loss. BMI was the only marker correlating with OS, only in stage 4 hypopharyngeal cancer patients. All three markers significantly correlated with survival among p16 positive oropharyngeal and glottic cancer patients. We found BMI, percent of weight loss and PNI good candidate markers for malnutrition. PNI proved to be superior in every aspect, enabling the treating physicians to discover high-risk patients in need of aggressive re-nourishment. The survival of supraglottic laryngeal squamous cancer patients seemed to be independent of these nutritional status markers, which observation should be a subject of further investigations.

Institution-level Patterns of Care for Early-stage Oropharynx Cancers in the United States.

The adoption of transoral robotic surgery and shifting epidemiology in oropharyngeal squamous cell cancer have stimulated debate over upfront and adjuvant treatment. Institutional variation in practice patterns can be obscured in patient-level analyses. We aimed to characterize institutional patterns of care as well as identify potential associations between patterns of care and survival. This was a retrospective cohort study of patients identified from 2004-2015 in the National Cancer Database. We analyzed 42,803 cases of oropharyngeal squamous cell cancer Stage cT1-2N0-2bM0 (AJCC 7th edition) treated with curative intent surgery and/or radiotherapy. We defined facility-4-year periods to account for changing institutional practice patterns. The 42,803 patients were treated within 2578 facility-4-year periods. We assessed institutional practice patterns, including the ratio of upfront surgery to definitive radiotherapy, case volumes, use of adjuvant therapies (radiotherapy or chemoradiotherapy), and margin positivity rates. Survival associations with institutional practice patterns were estimated with Cox regression. The ratio of upfront surgery to definitive radiotherapy ranged from 80-to-1 to 1-to-23. The institution-level median rate of adjuvant radiotherapy was 69% (IQR 50%-100%), adjuvant chemoradiotherapy was 44% (IQR 0%-67%), and margin-positive resection was 33% (IQR 0%-50%). On patient-level MVA, worse overall survival was not significantly associated with institutional case volume, adjuvant radiotherapy, or adjuvant chemoradiotherapy utilization. High rates of multimodal therapy and positive margins underscore the importance of multidisciplinary care and highlight variable patterns of care across institutions. Further work is warranted to explore indicators of high-quality care and to optimize adjuvant therapy in the HPV era.

Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience

Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs. We hypothesized that TSRT beyond 6 weeks may not portend poorer outcomes for the former. We identified nonmetastatic, high-risk HPV+ OPSCCs treated with multimodal therapy at 2 institutions. Prolonged TSRT was defined as >6 weeks and was evaluated for association with recurrence-free survival (RFS). Radiation treatment time (RTT; time from the first to the last day of RT), total treatment package time (TTPT; time from surgery to the end of adjuvant treatments), de-escalated RT (dose ≤56 Gy), concurrent chemotherapy, smoking history, and treatment institution were evaluated as possible confounders. In total, 96 patients were included. The median follow-up time was 62 months (4-123 months); 69 patients underwent transoral robotic surgeries, and 27 received open surgeries. The median postoperative RT dose was 60 Gy (50-70.8 Gy). The median TSRT, RTT, and TTPT were 38 days (11-208), 43 days (26-56 days), and 81 days (40-255 days), respectively. Ten patients failed treatment at a median of 8 months (4-64 months). Two locoregional and 4 distant failures occurred in the group without prolonged TSRT, whereas 2 locoregional and 2 distant failures were recorded in the prolonged TSRT group. Prolonged TTPT, de-escalated RT, chemotherapy, smoking history, and treatment institution were not associated with treatment failure. RTT was dropped from our analyses as no events appeared in the prolonged RTT group, and no reliable hazard ratio could be computed. TSRT > 6 weeks was not significantly associated with inferior outcomes in the postoperative management of HPV+ OPSCCs. Longer TSRT may facilitate better recovery from surgical toxicity, as needed, without compromising oncologic outcomes. The TSRT goal for these cancers should be investigated in future studies.

Proposals for the delineation of neck clinical target volume for definitive Radiation therapy in patients with oral/ oropharyngeal squamous cell cancer based on lymph node distribution

Purpose/Objective(s)To establish the distribution pattern of cervical lymph node metastasis (LNM) and propose optimized clinical target volume (CTV) boundaries specific to oral/ oropharyngeal squamous cell cancer (OSCC/OPSCC). Materials/Methods531 patients with pathologically confirmed OSCC/OPSCC were enrolled from January 2013 to June 2022. Patients were stratified into two groups based on the minimal distance from the lesion's edge to the body's midline: ≤1 cm or > 1 cm. The geometric center of cervical metastatic LN was marked on a template CT. LN distribution probability maps were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for CTV boundaries specific to OSCC/OPSCC. ResultsA total of 1962 positive LNs were enrolled. Compared with the > 1 cm group, the ≤ 1 cm group has following feature tendencies: male smokers, younger, median organs, large gross lesion, infiltrative growth pattern, contralateral LNM. The most frequently involved level of LNM was ipsilateral II, but ipsilateral Ib had the highest involvement rate in the > 1 cm OSCC group. In addition, tongue cancer had a higher incidence of LN extranodal extension (ENE), which mainly distributes in ipsilateral level II. The skip metastasis was prone to from level III to Vb (3.5 %) in LN(+)/ENE (-), and level Ib to VIa (3.7 %) in LN(+)/ENE (+). Accordingly, we proposed the following modifications: 1. only including lateral and posterior margin of submandibular gland within 5 mm; 2. retracting posterior boundary of level II to front edge of levator scapula muscle, and descending the upper boundary to transverse process of C2 vertebra only for OSCC; 3. including posterior third of thyroglossal muscle or anterior edge of sternocleidomastoid muscle; 4. sparing level Va in case of only level II involvement; 5. including upper area of the thyroid cartilage plate in case of level Ib LN(+)/ENE (+); 6. sparing level VIIa is considered. ConclusionThis is the first description of LN topographic spread patterns for OSCC/OPSCC. Modified CTV for prophylactic irradiation was proposed to spare the organs at risk and minimize adverse effects.

“Why am I still suffering?”: Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy

BackgroundLate effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck–specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives. MethodsThis work is part of the multicentre mixed method ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition), evaluating fatigue and neurocognitive function in patients following radiotherapy +/- chemotherapy for oropharyngeal cancer and impact on quality of life. Semi-structured interviews were conducted in adults treated with radiotherapy (+/-chemotherapy) for oropharyngeal squamous cell carcinoma >/=24 months from completing treatment. Reflexive thematic analysis performed. Results21 interviews (11 men and 10 women; median age 58 years and median time post-treatment 5 years) were conducted and analysed, yielding six themes: (1) unexpected burden of fatigue, (2) noticing changes in neurocognitive function, (3) the new normal, (4) navigating changes, (5)insufficient awareness and (6)required support. Participants described fatigue that persisted beyond the acute post-treatment period and changes in neurocognitive abilities across several domains. Paid and unpaid work, emotions and mood were impacted. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They reported lack of recognition of these late effects, being poorly informed and being unprepared. Follow-up services were thought to be inadequate. ConclusionsFatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Patients felt ill-prepared for these late sequelae, highlighting opportunities for improvement of patient information and support services.

Revisiting Feeding Tube Utilization in Oropharynx Cancer: 6-Year Prospective Registry Analysis.

Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients. Retrospective analysis of prospective cohort from 2015 to 2021. Single-institution NCI-Designated Comprehensive Cancer Center. With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI]). Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66]). In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration.

Role of transoral robotic surgery in the salvage setting: pitfalls and challenges

As rates of oropharyngeal squamous cell cancer (OPSCC) increase and patients survive longer, the number of patients with recurrence will also increase. Surgery is the primary tool for the management of locoregional recurrence when feasible, and transoral robotic surgery (TORS) techniques are a useful adjunct in effectively managing these cases. Careful patient selection, surgical planning, a thoughtful reconstructive plan, and postoperative supportive therapy are crucial for adequate oncologic and functional outcomes.

SAT255 Dual Cause Of Hypercalcemia: Can Both Multiple Myeloma And Paraneoplastic Parathyroid-related Hormone Production Occur Simultaneously?

Abstract Disclosure: A. Shah: None. A. Barnett: None. G. Elshimy: None. Introduction: Hypercalcemia has a broad differential of causes, while hypercalcemia of malignancy is critical to identify as it affects up to one in five cancer patients. Hypercalcemia of malignancy can be caused by the elevation of PTHrP, 1,25-dihydroxy vitamin D, or osteolytic lesions. Few cases reported in the literature combined local osteolytic hypercalcemia and humoral hypercalcemia of malignancy mechanisms in patients with multiple myeloma. We present a case of hypercalcemia due to two simultaneous malignancies: squamous cell carcinoma and multiple myeloma. Case: A 54-year-old African American female presented with altered mentation. She had a known diagnosis of oropharyngeal squamous cell cancer with lung metastasis since June 2022. At the time of evaluation in September 2022, she was actively on cetuximab chemotherapy and completed her initial radiation. Her labs showed a white blood cell count of 10,200 (4000-11000 cells/μL), hemoglobin 9 (12-14 gm/dL), creatinine 0.85 (0.7-1.4 mg/dL), calcium 14.7 (8.8-10.4 mg/dL), phosphorus 3.6 (2.9-5 mg/dL), albumin 2.5 (3.4-5.4 g/dL), total protein 11 (6-8.3 g/dL). She was treated with IV fluids, calcitonin, and IV bisphosphonates. A review of prior labs was significant for persistent mild hypercalcemia since August 2022 as well as serum protein 10 and albumin 3. Further evaluation was pursued which showed PTH 14.2 (11.1-79.5pg/ml), PTHrP 37 (less than 4.2 pmmol/L), 1,25-Vitamin D 24 (19.9-79.30 pg/ml), 25-Vitamin D 7.86 (25-80 ng/ml). Elevated protein-albumin gradient caused concern for multiple myeloma, so further investigation was performed. Serum protein electrophoresis had a monoclonal spike of 3.94 gm/dL, Kappa: Lambda light chain ratio of 18.94 (0.96-1.65), and a 24-hour urine protein of 172 mg. Bone marrow biopsy showed 80% plasma cells consistent with multiple myeloma. Skeletal survey did not show any lytic lesions. Her hypercalcemia was attributed to two simultaneously occurring malignancies given the elevated PTHrP and newly diagnosed multiple myeloma. The patient improved with medical management for the hypercalcemia and was started on dexamethasone for the multiple myeloma. Discussion: Hypercalcemia of malignancy is commonly associated with both liquid malignancies like multiple myeloma, leukemia, and lymphoma as well as solid malignancies of squamous cell origins. PTHrP is elevated in squamous cell and renal cell carcinomas while high 1,25-dihydroxy vitamin D is seen in lymphomas. Multiple myeloma causes hypercalcemia through cytokine secretion resulting in the activation of osteoclasts causing osteolytic lesions. Our patient had hypercalcemia due to high PTHrP from squamous cell carcinoma as well as newly diagnosed multiple myeloma. This case highlights the importance of recognizing that hypercalcemia may be multifactorial and a complete evaluation is needed to treat all causes appropriately. Presentation: Saturday, June 17, 2023

144P Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers

144P Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers

Patterns and distribution of regional nodal involvement and recurrence in a surgically treated oropharyngeal squamous cell carcinoma cohort at a tertiary center

ObjectivesTo investigate and describe the patterns of regional metastases and recurrences after surgical treatment of oropharyngeal squamous cell cancer (OPSCC). Materials and MethodsRetrospective study of patients diagnosed with OPSCC from 2006 to 2021 at a tertiary referral center. Only patients treated with surgery including a neck dissection were included. Patients with unknown human papillomavirus (HPV) status, prior head and neck cancer, distant metastases, or synchronous head and neck cancer were excluded. ResultsA total of 928 patients were included. 89% were males, the average age was 58.6 years (range: 25.2–87.5), 874 (94%) were HPV(+), and 513 (55.3%) had a tonsil cancer. Among cN + patients, the most commonly involved levels at presentation were level II (85.2%), level III (33.3%), and level IV (9.4%). In cN0 patients, metastases were only observed in level II (16.2%) and level III (9.2%). Nodal recurrence occurred in 48 (5.2%) patients after a median time of 1.0 years (interquartile range: 0.6–2.0). Nodal recurrence incidence was similar in HPV(+) and HPV(-) patients (5.0% vs. 7.4%, p = 0.44). The most common levels for regional recurrence were ipsilateral level II (45.8%), contralateral level II (43.8%), and ipsilateral level V (25.0%). Multivariable analysis revealed that pN was a significant predictor for regional recurrence (p = 0.02). ConclusionThere is no difference in the distribution of regional metastases and recurrences in HPV(+) and HPV(-) OPSCC patients. Our findings align with the established understanding that regional metastases predominantly manifest in the ipsilateral level II-IV at presentation. Moreover, the data support the clinical recommendation to restrict elective neck dissection in cN0 patients to ipsilateral levels IIa and III, excluding level IIb. Regional recurrence is significantly associated with pN status.

Intensity-Modulated Radiation Therapy Alone Versus Intensity-Modulated Radiation Therapy and Brachytherapy for Early-Stage Oropharyngeal Cancers: Results From a Randomized Controlled Trial

The objective of this study was to compare clinical outcomes of intensity-modulated radiation therapy (IMRT) alone versus IMRT + brachytherapy (BT) in patients with T1-T2N0M0 oropharyngeal squamous cell cancers (OPSCC). This open-label randomized controlled trial was conducted at Tata Memorial Hospital, Mumbai, India. Patients with stage I and II OPSCC were considered for IMRT to a dose of 50 Gy/25 fractions/5 weeks in phase I followed by randomization (1:1) to further treatment with IMRT (20 Gy/10 fractions/2 weeks) or BT (192Ir high dose rate, 21 Gy/7 fractions/2 fractions per day). The primary endpoint of the trial was the reduction in xerostomia at 6 months evaluated using 99mTc salivary scintigraphy. Severe salivary toxicity (xerostomia) was defined as posttreatment salivary excretion fraction ratio <45%. Secondary endpoints were local control, disease-free survival, and overall survival. Between November 2010 and February 2020, 90 patients were randomized to IMRT (n = 46) alone or IMRT + BT (n = 44). Eleven patients (8 residual/recurrent disease, 2 lost to follow-up, 1 second primary) in the IMRT arm and 9 patients (8 residual/recurrence, 1 lost to follow-up) in the BT arm were not evaluable at 6 months for the primary endpoint. At 6 months, xerostomia rates using salivary scintigraphy were 14% (5/35: 95% CI, 5%-30%) in the BT arm while it was seen in 44% (14/32: 95% CI, 26%-62%) in the IMRT arm (P = .008). Physician-rated Radiation Therapy Oncology Group grade ≥2 xerostomia at any time point was observed in 30% of patients (9/30) in the IMRT arm and 6.7% (2/30) in the BT arm (P = .02). At a median follow-up of 42.5 months, the 3-year local control in the IMRT arm was 56.4% (95% CI, 43%-73%) while it was 66.2% (95% CI, 53%-82%) in the BT arm (P = .24). The addition of BT to IMRT for T1-T2N0M0 OPSCC results in a significant reduction in xerostomia. This strongly supports the addition of BT to IMRT in suitable cases.

Predicting HPV association using deep learning and regular H&E stains allows granular stratification of oropharyngeal cancer patients

Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) represents an OPSCC subgroup with an overall good prognosis with a rising incidence in Western countries. Multiple lines of evidence suggest that HPV-associated tumors are not a homogeneous tumor entity, underlining the need for accurate prognostic biomarkers. In this retrospective, multi-institutional study involving 906 patients from four centers and one database, we developed a deep learning algorithm (OPSCCnet), to analyze standard H&E stains for the calculation of a patient-level score associated with prognosis, comparing it to combined HPV-DNA and p16-status. When comparing OPSCCnet to HPV-status, the algorithm showed a good overall performance with a mean area under the receiver operator curve (AUROC) = 0.83 (95% CI = 0.77-0.9) for the test cohort (n = 639), which could be increased to AUROC = 0.88 by filtering cases using a fixed threshold on the variance of the probability of the HPV-positive class - a potential surrogate marker of HPV-heterogeneity. OPSCCnet could be used as a screening tool, outperforming gold standard HPV testing (OPSCCnet: five-year survival rate: 96% [95% CI = 90–100%]; HPV testing: five-year survival rate: 80% [95% CI = 71–90%]). This could be confirmed using a multivariate analysis of a three-tier threshold (OPSCCnet: high HR = 0.15 [95% CI = 0.05–0.44], intermediate HR = 0.58 [95% CI = 0.34–0.98] p = 0.043, Cox proportional hazards model, n = 211; HPV testing: HR = 0.29 [95% CI = 0.15–0.54] p < 0.001, Cox proportional hazards model, n = 211). Collectively, our findings indicate that by analyzing standard gigapixel hematoxylin and eosin (H&E) histological whole-slide images, OPSCCnet demonstrated superior performance over p16/HPV-DNA testing in various clinical scenarios, particularly in accurately stratifying these patients.

Costs of oropharyngeal squamous cell cancer treatment in Finland

BackgroundOropharyngeal squamous cell carcinoma (OPSCC) can be treated with definitive (chemo)radiotherapy ((C)RT) or primary surgical treatment (PST) with or without postoperative oncologic treatment. The prognosis of OPSCC does not essentially depend on the treatment modality, which allows to consider secondary decision-making aspects such as treatment costs when recommending an individual treatment modality. We attempted to analyze the costs associated with definitive (C)RT and PST in the treatment of OPSCC in Finland.Materials and methodsWe included 73 patients diagnosed with OPSCC at the Helsinki University Hospital (HUS) (Helsinki, Finland) in 2019 and 2020. Treatment costs were defined as the costs incurred in the specialized medical care during the first 12 months after the diagnosis was established.ResultsDefinitive RT and definitive CRT were on a 1-year horizon associated with median costs of approximately 10 700€ and 13 300€, respectively; while, the median costs of PST equaled about 40 600€. The costs of definitive (C)RT mostly consisted of the costs of (chemo)radiotherapy sessions; while, the operating room costs and the costs of intensive care and stay on a ward drove the costs of PST.ConclusionsPST is associated with 2–3 times higher median costs than definitive (C)RT in Finland. The finding differs from the results previously reported in North America, which is related, e.g., to differences in the treatment practices as well as in the regulation of the health care systems.

Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer

Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers. To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer. This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022. The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning). The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival. A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms. This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates. ClinicalTrials.gov Identifier: NCT01874587.

Incidence, trends, and survival of oropharyngeal squamous cell cancer in Aotearoa New Zealand, 2006–2020

BackgroundAn increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity. MethodsThe study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates. ResultsThe average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50–69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946–50 and that of 1956–60. The increase in incidence was seen in Māori and Pākehā/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006‐13 to 78% in 2014–20. Survival rates were lower in older patients, females, and Māori patients. ConclusionThis study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Māori and Pākehā/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.

The role of etiopathogenesis in shaping local immune responses in squamous cell oropharyngeal cancer

Актуальность. Установлено, что несмотря на инфильтрацию опухоли иммунокомпетентными клетками, зачастую плоскоклеточный рак головы шеи (ПРГШ) демонстрирует именно иммуносупрессивный тип микроокружения, что влияет на результаты лечения и диктует поиск новых прогностических маркеров и мишеней терапии. Цель исследования. Изучить состав иммунных клеток при орофарингеальном плоскоклеточном раке (ОФПКР) и тип экспрессии PD-L1 (CPS, TPS) в зависимости от ВПЧ-статуса, пола и возраста. Материалы и методы. В исследование кафедры онкологии КубГМУ на базе ГБУЗ КОД №1, г. Краснодара, с 2020 г. до июня 2022 г. включено 65 р16-негативных (52 %) и 60 р16-позитивных (48 %) больных ОФПКР. У 86 пациентов выполнена оценка уровня TILs, при иммуногистохимическом анализе изучены компоненты иммунного микроокружения по маркерам CD4, CD8, CD68, CD163, CD20, экспрессия PD-L1. Статистический анализ выполнен с использованием статистического пакета IBM SPSS Statistics v. 22. Результаты. ВПЧ-позитивный статус ассоциирован с раком нёбных миндалин (р = 0,021), более высоким уровнем опухоль-инфильтрирующих лимфоцитов (TILs) (p = 0,007), вероятно, за счёт Тregs ввиду более достоверной связи с CD4+ TILs (р = 0,007), чем с CD8+ TILs (р = 0,033). ОФПКР у женщин в сравнении с мужчинами чаще представлен раком миндалин (р ˂ 0,001), характеризуется высокими значениями CD4+ TILs (р = 0,021) и CD8+ TILs (р = 0,035), однако более высоким иммунорегуляторным индексом (ИРИ) CD4/CD8 (р = 0,021). У женщин установлен более высокий уровень экспрессии PD-L1 на опухолевых клетках (TPS) (р = 0,009) и комбинированный показатель (CPS) (р = 0,018), чем у мужчин. Более высокие значения CPS и TPS выявлены при CD4+TILs ˂ 30 % (р = 0,001, р = 0,005 соответственно) и при CD68 ˂ 8,5 % (р = 0,001). N+ связано с высоким уровнем CPS PD-L1. У ВПЧ-позитивных больных выявлен более высокий уровень экспрессии маркера CD20+В-лимфоцитов (р = 0,02) в группе моложе 55 лет и уровень CD4+TILs ≥ 30 ассоциирован с более высокими значениями CD20 (р = 0,002). Заключение. Тип формирования микроокружения ОФПКР и степень иммунной супрессии различается в зависимости от пола, возраста, ассоциации с транскрипционно активной ВПЧ-инфекцией.

Active upper aerodigestive tract hemorrhage in patients with head and neck cancers: the “dot-in-sludge” sign

Active extravasation into the upper aerodigestive tract is a dramatic and potentially life-threatening complication in patients with head and neck cancers. It prompts presentation to the emergency room and subsequent urgent imaging to identify the source of hemorrhage. Imaging of these patients may be complicated by treatment-altered anatomy, posing a challenge to the emergency radiologist who needs to rapidly identify the presence of active hemorrhage and the potential source vessel. This retrospective review summarizes the clinical and imaging findings of 6 oropharyngeal and oral cavity squamous cell cancer (SCC) patients with active upper aerodigestive tract hemorrhage. Most patients had advanced stage disease and prior radiation therapy. All CECT or CTA exams on presentation demonstrated the “dot-in-sludge” sign of active extravasation, as demonstrated by a “dot” of avidly enhancing extravasated contrast material layered against a background “sludge” of non-enhancing debris in the lumen of the upper aerodigestive tract. Common sources of hemorrhage included the lingual, facial, and superior thyroidal arteries. Familiarity with these findings will help radiologists increase their accuracy and confidence in interpreting these urgent, complex examinations.

Intraoperative Imaging Techniques to Improve Surgical Resection Margins of Oropharyngeal Squamous Cell Cancer: A Comprehensive Review of Current Literature.

Inadequate resection margins in head and neck squamous cell carcinoma surgery necessitate adjuvant therapies such as re-resection and radiotherapy with or without chemotherapy and imply increasing morbidity and worse prognosis. On the other hand, taking larger margins by extending the resection also leads to avoidable increased morbidity. Oropharyngeal squamous cell carcinomas (OPSCCs) are often difficult to access; resections are limited by anatomy and functionality and thus carry an increased risk for close or positive margins. Therefore, there is a need to improve intraoperative assessment of resection margins. Several intraoperative techniques are available, but these often lead to prolonged operative time and are only suitable for a subgroup of patients. In recent years, new diagnostic tools have been the subject of investigation. This study reviews the available literature on intraoperative techniques to improve resection margins for OPSCCs. A literature search was performed in Embase, PubMed, and Cochrane. Narrow band imaging (NBI), high-resolution microendoscopic imaging, confocal laser endomicroscopy, frozen section analysis (FSA), ultrasound (US), computed tomography scan (CT), (auto) fluorescence imaging (FI), and augmented reality (AR) have all been used for OPSCC. NBI, FSA, and US are most commonly used and increase the rate of negative margins. Other techniques will become available in the future, of which fluorescence imaging has high potential for use with OPSCC.

Anti-PD‑1-induced type 1 diabetes mellitus in patient with recurrent oropharyngeal squamous cell cancer

Immune checkpoint inhibitors targeting a programmed cell death ligand (PD-L1) have been a major breakthrough in the treatment of many cancers . Nivolumab is an antibody that selectively blocks the PD‑1 receptor on the surface of cytotoxic T- cells to prevent downregulation of the immune response . Immune checkpoint inhibitors can cause immune-related adverse events , including endocrine ones . Type 1 diabetes mellitus is one of the severe rare and potentially lethal immune-related adverse events diagnosed in less than 1% of patients receiving immune checkpoint inhibitors . The total incidence of type 1 diabetes mellitus associated with the PD‑1 inhibitor is relatively low ; however , it develops rapidly and is potentially life-threatening without timely diagnosis and treatment . Since PD‑1 inhibitors are widely used in cancer treatment , complications such as type 1 diabetes mellitus should attract medical attention . During treatment , specialists should help patients better recognize the symptoms of hyperglycemia or diabetic ketoacidosis , which requires careful observation , regular monitoring of blood glucose levels , rapid detection and correct diagnosis and treatment of diabetes mellitus .

Value of routine follow-up in oropharyngeal squamous cell cancer patients treated with curative intent.

The major goal of routine follow-up in oropharyngeal squamous cell carcinoma (OPSCC) patients is the asymptomatic detection of new disease in order to improve survival. This study evaluated the effect of routine follow-up on overall survival (OS). A retrospective cohort of 307 consecutive OPSCC patients treated with curative intent between 2006 and 2012 was analyzed. The effectiveness of routine follow-up was studied by comparing treatment-intent and OS in patients with asymptomatically versus symptomatically detected new disease. Three- and five-year risks of new disease were 29% (95% CI: 24-34) and 33% (95% CI: 27-39). Of the 81 patients with locoregional recurrence or second primary head and neck cancer, 8 (10%) were detected asymptomatically with no difference in OS with those detected with symptoms. Asymptomatic detection of new disease during routine visits was not associated with improved OS. The focus of follow-up should be on providing psychosocial care and rehabilitation.