Stage IVA Disease Research Articles

Premature adoption of adjuvant chemotherapy for locally advanced cervical carcinoma before the OUTBACK trial: cautionary tale on outcomes.

The aim of this study was to investigate the use and outcomes of adjuvant chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation. The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IVA disease who underwent definitive chemoradiation were selected. Patients who received radio-sensitizing single agent chemotherapy and those who received adjuvant multi-agent chemotherapy were identified. Overall survival was evaluated following generation of Kaplan-Meier curves while a Cox model was constructed to control for confounders. A total of 9895 patients were identified; 1003 (10.1%) received multi-agent adjuvant chemotherapy. Patients who received adjuvant chemotherapy were less likely to receive brachytherapy (60.9% vs 68.4%, p<0.001). Rate of adjuvant chemotherapy was higher among patients with stage IVA (18.1%) and stage III (11.9%) disease compared with those with stage II (8.4%) and stage IB2 (7.2%) disease (p<0.001). After controlling for confounders, administration of adjuvant chemotherapy was not associated with a survival benefit (hazard ratio 1.09, 95% confidence interval 0.98 to 1.20). Following stratification by disease stage, there was no survival benefit of patients who received adjuvant chemotherapy compared with those who did not; stage IB (p=0.002; 5 year overall survival 59.2% vs 74.9% favoring chemoradiation alone), stage II (p=0.41; 5 year overall survival 63.8% vs 67.6%, respectively), stage III (p=0.52; 5 year overall survival 48% vs 47.8%, respectively), or stage IVA disease (p=0.27; 5 year overall survival 29.5% vs 34.3%, respectively). In the US, approximately 1 in 10 patients with locally advanced cervical carcinoma who underwent definitive chemoradiation also received adjuvant chemotherapy that was not associated with improvement in overall survival.

PO0234: Outcomes of Exclusive Use of Magnetic Resonance Image-Guided Brachytherapy in Locally Advanced Cervical Cancer with a Focus on Stage IVa Disease

PO0234: Outcomes of Exclusive Use of Magnetic Resonance Image-Guided Brachytherapy in Locally Advanced Cervical Cancer with a Focus on Stage IVa Disease

Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial

Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35. Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer. Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.

Carbon-Ion Radiation therapy for Adenocarcinoma of the Uterine Cervix: Clinical Outcomes of a Multicenter Prospective Registry-Based Study in Japan (2016-2020)

Cases of adenocarcinoma of the uterine cervix (AUC) have poorer prognoses than those of squamous cell carcinoma. Carbon-ion radiation therapy (CIRT) outcomes for AUC have been reported in retrospective or single-institutional prospective studies but not prospective multicenter studies. We present the results of CIRT for AUC in a prospective multicenter study using a nationwide hospital-based registry in Japan. Patients with locally advanced untreated AUC who received CIRT at 4 Japanese centers between June 2016 and April 2020 were included in this study. In the absence of organ dysfunction, up to 5 weekly 40 mg/m2 cisplatin courses were administered. The primary endpoints were 2-year overall survival and local control rates. The secondary endpoints were 2-year disease-free survival rate and late adverse events (AEs). Forty-two patients were enrolled with a median age of 54 years (range, 34-76 years). Patients were diagnosed with stage IIB (n = 26), IIIB (n = 12), or IVA (n = 4) disease. The median follow-up period was 24 months. The 2-year overall survival, local control, and disease-free survival rates were 97.5% (95% CI, 92.7%-100.0%), 80.9% (95% CI, 66.9%-94.8%), and 64.3% (48.1%-80.4%), respectively. Two patients developed grade 3 rectum/sigmoid AE. One patient required urinary diversion surgery during a salvage operation for local tumor recurrence (grade 3 genitourinary AE). No other grade 3 or worse toxicities were reported. CIRT is an effective treatment for locally advanced AUC. Further research is required to validate the safety and efficacy of CIRT for AUC.

Sintilimab combined with definitive chemoradiotherapy in locally advanced esophageal squamous cell carcinoma: A single-arm, multicenter, phase 2 trial.

e16120 Background: Sintilimab is a PD-1 inhibitor that is approved for the treatment of advanced esophageal squamous cell carcinoma, but its efficacy and safety in locally advanced disease is unclear. We administered sintilimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the efficacy and safety of this treatment pattern. Methods: We conducted a multicenter, phase 2 trial at three cancer centers in sichuan province. Patients aged 18-75 years with untreated, unresectable, stage II-IVA esophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (60·0 Gy in 30 fractions), chemotherapy (two cycles of intravenous Albumin-Bound Paclitaxel [180 mg/m2, day1] and cisplatin [25 mg/m2, day1-3]), and Sintilimab (200 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate, quality of life (not reported here), and safety. The trial is registered with ClinicalTrials.gov, NCT046 02013. Enrolment is completed and follow-up is ongoing. Results: Between Oct 19, 2020, and Dec 08, 2023, 52 patients were enrolled. The median age was 65 years (IQR 58-71), 11 (21.1%) of 52 patients had stage IVA disease, and 49 (94.2%) patients were male and 3 (5.8%) were female. 50 (96.2%) of 52 patients patients completed the planned chemoradiotherapy. After a median follow-up of 15.0 months (IQR 7·9-28·0), the median PFS was not reached. The 1-, 2- and 3-year OS rates were 93.7%, 84.0% and 45.0%, respectively.The most common grade 3 or worse adverse event was neutropenia (23 [44.2%] of 52). Eight (15.4%) had treatment-related pneumonitis, but no patient died. Conclusions: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation. Clinical trial information: NCT04602013 .

Surgical treatment of thymic epithelial tumors: a narrative review.

Thymic epithelial tumors (TETs) are scarce neoplasms of the prevascular mediastinum. Included in this diverse category of lesions are thymomas and thymic carcinomas (TCs). Surgery is the mainstay of treatment of tumors that are deemed resectable. However, up till now, optimal surgical access has been a subject of debate. The advent of new techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS), challenged the median sternotomy which was traditionally considered the access of choice. This review aims to demonstrate the current evidence concerning the surgical treatment of TET and to enlighten other controversial issues about surgery. PubMed research was conducted using the terms [surgery] AND [thymic epithelial tumors] OR [thymomas] and [surgical treatment] AND [thymic epithelial tumors] OR [thymomas]. Papers concerning pediatric cases and non-English literature papers were excluded. Individual case reports were also excluded. Minimally invasive surgical techniques (MIST) such as VATS and RATS are increasingly applied in early-stage TET. Although numerous published studies have demonstrated better perioperative outcomes in early-stage TET, long-term follow-up data are still required to demonstrate the oncological equivalent of MIST to open surgery. Resection of stage III TET is more challenging. Thymectomy can be expanded en bloc to include the major vascular structures, lung, pleura, phrenic, or vagus nerve in these individuals. There is no agreement on the ideal surgical access and traditionally these patients underwent open sternotomy, sometimes combined with a thoracic access. Evidence concerning the treatment of stage IVA disease is mainly derived from retrospective case series which are highly heterogeneous in terms of the number of enrolled patients, histology, degree of pleural involvement, and timing of presentation. New techniques in the field of minimally invasive surgery are gaining acceptance for early-stage TET but longer follow-up periods are warranted to prove their oncological outcomes. On the contrary, these techniques should be used cautiously in case of locally advanced tumors. Surgeons must not forget that the main objective is the complete resection of the lesion, which is one major predictive factor for increased survival.

Efficacy and Safety of Postoperative Adjuvant Radiation Therapy in Resected Nasal Cavity and Paranasal Sinus Mucosal Melanoma: A Combined Analysis

BackgroundMucosal melanoma of the nasal cavity and paranasal sinuses (NPMM) is a highly aggressive disease. The role of postoperative adjuvant radiotherapy is controversial. MethodsA total of 300 patients with NPMM treated between March 2009 and January 2020 were divided into SA (surgery alone, 158 patients) and SR (surgery plus radiotherapy, 142 patients) groups. Postoperative radiotherapy was recommended, with a total dose of 65–70 Gy/30–35 fx to the GTV (gross tumor volume) and 60 Gy/30 fractions to the CTV (clinical target volume). The primary endpoint was relapse-free survival (RFS). Secondary endpoints included local-recurrence-free survival, distant metastasis-free survival (DMFS), and overall survival (OS). ResultsAt a median follow-up of 50.0 months, RFS in the SA and SR groups was 9.8 and 15.2 months (HR: 0.714, 95% CI: 0.546–0.933, P = 0.014). DMFS in SA and SR groups was 23.8 and 21.3 months (HR: 0.896, 95% CI: 15.7–31.9 vs. 13.3–29.3, P = 0.457). OS in SA and SR groups was 31.0 and 35.1 months (HR: 0.816, 95% CI: 25.7–36.3 vs. 27.1–43.2, P = 0.178). For patients with stage IVA NPMM, radiotherapy reduced the incidence of relapse by 0.43-fold. ConclusionsPostoperative radiotherapy played a crucial role in the local control of resected NPMM, especially in patients with stage T4a or IVA disease.

Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database.

Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy (ST). We sought to determine whether resection of the primary tumor was associated with overall survival (OS) in a multicentric cohort of patients with single-site synchronous oligometastatic non-small cell lung cancer. Using the National Cancer Database (2018 to 2020), we evaluated patients with clinical stage IVA disease who received ST and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity score-matched analysis to study factors associated with S (logistic regression) and OS (Cox regression and Kaplan-Meier), respectively. Among 12,215 patients identified, 2.9% (N = 349) underwent S and 97.1% (N = 11,886) ST (chemotherapy or immunotherapy) without surgery. Patients who underwent S were younger, more often White, had higher income levels, were more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N = 80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox regression, S and resection of the metastatic site were associated with improved survival (hazard ratio 0.67, 95% CI 0.56 to 0.80 and hazard ratio 0.80, 95% CI 0.72 to 0.88, respectively). After propensity matching, OS was improved in patients undergoing S (median 36.8 vs 20.8 months, log-rank p < 0.001). Advances in ST for non-small cell lung cancer may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved OS in selected patients with single-site oligometastatic disease.

Definitive Chemoradiotherapy for Salivary Gland Cancers

Surgical resection is the standard of care for salivary gland tumors of the head and neck. The role of radiotherapy is typically reserved for the adjuvant setting in those patients with high risk factors on surgical pathology. Surgical resection in some cases may lead to significant impairment in speech or swallowing due to location of the primary tumor. In other cases, patients may not be medically able to receive an oncologic resection. Our institution has developed a protocol for organ preservation for well-selected salivary gland malignancies. Here we report disease outcomes of salivary gland cancer patients treated with definitive chemoradiotherapy. We retrospectively reviewed all salivary gland cancer patients at our institution who received definitive chemoradiation from January 1990 to December 2019. Chemoradiation typically consisted of 4 to 6 alternating weekly cycles of paclitaxel (100 mg/m2 on d1), infusion 5-fluorouracil (600 mg/m2/d on d0-5), hydroxyurea (500 mg PO BID), and either 1.8 Gy or 2 Gy daily or 1.5 Gy twice-daily irradiation followed by a 9-day treatment break (TFHX). The Kaplan-Meier method was used to estimate rates of locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). Nineteen patients met eligibility criteria and were included for analysis. 53% of patients had adenoid cystic histology. Salivary duct, mucoepidermoid, acinic cell, and myoepithelial histologies each were represented by 10.5% of patients. About 26% of tumors were located in the nasopharynx, 21% in the base of tongue and 26% in the parotid. 74% of the patients were node negative and 53% of patients had stage IVA disease. T3 disease occurred in 26.3% while T4a and T4b disease occurred in 31.6% each. Median follow-up was 45.8 (IQR: 29-66) months. 47% of patients were treated using a twice daily approach, while 53% were treated with daily fractionation with a median dose of 72 Gy (IQR: 70-75). Three-year locoregional control (LRC), distant-metastasis free survival (DMFS), and overall survival (OS) were 93%, 76%, and 81% respectively. Eight of nine distant failures had T4a/T4b disease. Accounting for competing risk of death, local failure was 5.6% at three years. The most common acute complications were grade 2-3 mucositis (74%) and skin toxicity (47%). One patient discontinued chemoradiation due to severe hand foot mouth syndrome. 42% of patients had late toxicity of xerostomia. Promising organ preservation is seen with concurrent chemoradiation for salivary gland cancer patients. Further prospective study of organ preservation in salivary gland cancers is warranted.

Optimum Radiation Dose for Palliation in Head and Neck SCC: A Phase III Randomized Controlled Trial (OPRAH)

Palliative radiotherapy has been used to alleviate symptoms in locally advanced (T4b) head and neck Squamous cell carcinoma, but optimum dose is still debated. The trial has been designed to determine if high palliative radiation dose (30 Gy/ 5#/ 5 days) improves progression free survival compared to low palliative dose (20 Gy/ 5# 5 days). The secondary objective was to compare toxicity rates profile between the two radiation doses (CTCAE version 5) and compare Quality of life between the two arms with QOL - HN35 questionnaire. This is a prospective randomized phase III randomized controlled trial. We hypothesized that by increasing the dose per fraction and total dose there would be an improvement in PFS without difference in late toxicity and QOL. The present study will also perform an exploratory analysis of effect of palliative radiotherapy on immune function and its effect on survival. Considering median PFS 2.5 months in 20 Gy arm we assumed that PFS will improve by 1.25 months (total PFS 3.75 months) in 30 Gy arm. To reach the hypothesis with 90% power and alpha error of 0.05, attrition rate of 10% sample size calculated was 286. Patients with cT4b disease of larynx/ Hypopharynx/ Oropharynx/ Oral cavity not amenable to surgery, Carotid encasement > 180 degree, histologically proven squamous cell carcinoma, Age > 18 years and < 75 years ECOG PS 0-2 were eligible. Until December 2022, we completed accrual of 239 patients. Median age: 53 years (Range: 29-70 years); Gender: Male: Female = 9: 1 (214: 25). 145 patients had history of smoking, 87 had additional history of tobacco chewing. 67 patients had history of alcohol consumption, 13 patients had history of smoking, tobacco and alcoholism. All patients had stage IVA or Stage IVB disease. Primary site was oral cavity in 58%, Oropharynx in 19%, larynx in 10% and hypopharynx in 8% cases. 72.3% patients had a PS of 1, 21.7% had PS 2 at presentation. Prior to RT requirement of analgesic was: No pain medicine: 5; WHO step I:173, WHO step II: 52, WHO step III:14. All patients received conformal radiation with 6 MV linear accelerator. Target volume was GTV plus 1 cm margin to form CTV and 5 mm expansion to generate PTV. Out of 239 patients 67 patients had a disease progression. Mucositis is the commonest side effect affecting most of the patients and improve with best supportive care. High dose palliation appears to be equally well tolerated. However, the impact of such dose escalation will be established if final analysis reaches the pre-defined endpoint.

Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for Patients with Pleural Metastases from Thymic Malignancies

Pleural metastases are common sites for recurrence and progression in patients with thymic malignancies. The management of pleural metastases typically involves surgical resection with or without neoadjuvant or adjuvant systemic therapy. After surgical resection of pleural metastases, the 5-year progression-free survival (PFS) rate is about 29-45%. While radiation therapy (RT) is standardly used in the management of locally-advanced thymic malignancies, the role of RT in patients with pleural metastases in unclear. Intensity-modulated pleural radiation therapy (IMPRINT) is a RT technique currently being used to treat malignant pleural mesothelioma (MPM) patients with 2 intact lungs at centers that specialize in MPM treatment. This IMPRINT technique can potentially be extrapolated to thymic patients with pleural metastases. Because the risk of toxicity is of greater concern for thymic patients given their overall relatively favorable prognosis, the rate of toxicity, particularly radiation pneumonitis, needs to be established in the thymic patient population. This is a single-arm, single institution Phase II study of hemithoracic IMPRINT for patients with pleural metastases from thymic malignancies. The primary endpoint of this study is grade 3 or higher radiation pneumonitis within 4 months of completing RT. Secondary endpoints include any toxicity, progression-free survival, patterns of failure and overall survival. Patients must have a pathologically confirmed diagnosis of a thymic malignancy with radiologic or pathologic evidence of pleural metastases. Thymoma or thymic carcinoma are allowed. Patients may have de novo stage IVA disease or recurrent disease in the pleura. There must be no evidence of extrathoracic metastatic disease or contralateral pleural/pericardial disease. Surgical resection of the pleural nodules (ex: pleurectomy/decortication, debulking/metastasectomy) are allowed. Extrapleural pneumonectomy is not allowed. Patients are excluded if they have undergone prior thoracic radiation therapy preventing hemithoracic pleural IMRT, whereas prior thymic bed radiation and/or prior pleural SBRT are allowed. RT will be administered to the ipsilateral pleura to 50.4 Gy in 28 fractions. An optional dose-painting boost to gross disease up to 60 Gy while respecting normal tissue constraints is allowed. Patients can be treated with photon or proton therapy. Simulation, contouring and RT planning guidelines have been developed. Patients will be followed per protocol at regular intervals for at least 12 months following RT. The expected accrual is 36 patients over 4 years. Further information can be found on clinicaltrials.gov (NCT05354570). To be determined. To be determined.

Phase II study of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) for patients with pleural metastases from thymic malignancies.

TPS8616 Background: Pleural metastases are common sites for recurrence and progression in patients with thymic malignancies. The management of pleural metastases typically involves surgical resection with or without neoadjuvant or adjuvant systemic therapy. After surgical resection of pleural metastases, the 5-year progression-free survival (PFS) rate is about 29-45%. While radiation therapy (RT) is standardly used in the management of locally-advanced thymic malignancies, the role of RT in patients with pleural metastases in unclear. Intensity-modulated pleural radiation therapy (IMPRINT) is a RT technique currently being used to treat malignant pleural mesothelioma (MPM) patients with 2 intact lungs at centers that specialize in MPM treatment. This IMPRINT technique can potentially be extrapolated to thymic patients with pleural metastases. Because the risk of toxicity is of greater concern for thymic patients given their overall relatively favorable prognosis, the rate of toxicity, particularly radiation pneumonitis, needs to be established in the thymic patient population. Methods: This is a single-arm, single institution Phase II study of hemithoracic IMPRINT for patients with pleural metastases from thymic malignancies. The primary endpoint of this study is grade 3 or higher radiation pneumonitis within 4 months of completing RT. Secondary endpoints include any toxicity, progression-free survival, patterns of failure and overall survival. Patients must have a pathologically confirmed diagnosis of a thymic malignancy with radiologic or pathologic evidence of pleural metastases. Thymoma or thymic carcinoma are allowed. Patients may have de novo stage IVA disease or recurrent disease in the pleura. There must be no evidence of extrathoracic metastatic disease or contralateral pleural/pericardial disease. Surgical resection of the pleural nodules (ex: pleurectomy/decortication, debulking/metastasectomy) are allowed. Extrapleural pneumonectomy is not allowed. Patients are excluded if they have undergone prior thoracic radiation therapy preventing hemithoracic pleural IMRT, whereas prior thymic bed radiation and/or prior pleural SBRT are allowed. RT will be administered to the ipsilateral pleura to 50.4 Gy in 28 fractions. An optional dose-painting boost to gross disease up to 60 Gy while respecting normal tissue constraints is allowed. Patients can be treated with photon or proton therapy. Simulation, contouring and RT planning guidelines have been developed. Patients will be followed per protocol at regular intervals for at least 12 months following RT. The expected accrual is 36 patients over 4 years. Further information can be found on clinicaltrials.gov (NCT05354570). Clinical trial information: NCT05354570 .

Association between depressive symptoms and socioeconomic status in head and neck cancer patients attending rural tertiary health care center.

To study the association between depressive symptoms and socio-economic status (SES) in patients with head and neck cancer (HNC). Histopathology-proven non-metastatic and non-recurrent HNC patients attending radiation oncology services in February and June 2021 who consented to the study were evaluated with an interview. Hamilton Depression Rating Scale (HDRS) and modified BG Prasad classification were used to assess depressive symptoms and SES, respectively. Statistical analysis was done using SYSTAT version 12 (by Crane's software, Bangalore). The study cohort comprised 100 patients. The median age was 55 years (minimum: 28, maximum: 86) with a male-to-female ratio of 2.57:1. The majority of patients were educated beyond middle-school level (44%), of middle SES (47%), oral cavity subsite (68%), stage IVA (36%) disease, and were on treatment (79%). HDRS scores showed absent, moderate, and severe depressive symptoms in 21, 63, and 16 patients, respectively, that is, the prevalence of depressive symptoms was 79%. Lower socioeconomic strata showed a significantly higher prevalence of severe depressive symptoms (P-value = 0.01). HDRS score was significantly higher in females (P-value = 0.024) and in patients who were illiterate or were educated less than middle-school level (P-value = 0.010). No statistically significant difference was found between HDRS score and age of patient, stage and site of disease, and on treatment or follow-up status. Depressive symptoms are common in patients with head and neck cancer. Low socioeconomic status (SES), female gender, and education less than middle school are associated with severe depressive symptoms. Psycho-oncological and psychotherapeutic interventions are the need of the hour.

Lymph Node Metastasis and Patterns of Recurrence in Vulvar Carcinoma: 10 Years' Single Center Experience.

Vulvar carcinoma is a relatively rare malignancy and there is a paucity of data, especially from India and other developing countries regarding the prognostic factors impacting recurrence and survival. A retrospective observational study was conducted in the Department of Gynecologic Oncology at a tertiary care, regional cancer institute, including all patients with carcinoma vulva who underwent surgery between 2009 and 2018. Demographic profile, surgical-pathological information, details of neo-adjuvant chemotherapy, adjuvant radiation and chemotherapy, and peri-operative complications were analyzed. Long-term follow-up data was gathered, with an evaluation of various prognostic factors impacting recurrence and overall survival outcome. Forty-five cases with mean age of 56.2years (range 29-82) were treated during the study period. Surgery was the initial treatment modality in 41 (91.1%) cases. Neo-adjuvant chemotherapy prior to surgery was given to four cases. After complete surgico-pathological staging, most patients had stage I disease (26 cases, 57.8%) and 22.2% had stage II disease. Owing to microscopic lymph node involvement, seven cases (15.6%) belonged to FIGO stage III disease. Two cases had stage IVA disease with fixed groin nodes. Adjuvant chemotherapy in the form of 5-fluoro uracil and cisplatin was administered to four out of the nine patients with nodal involvement. The remaining five were advised adjuvant groin radiation. At a median follow-up of 34months (range 2-114months), 12 cases (26.7%) experienced a recurrence and one case with stage IVA disease progressed during adjuvant chemotherapy. The 5-year overall survival was 76.6% and the 5-year disease-free survival was 69.6%. There were a total number of 10 deaths, of which seven were due to disease recurrence or progression and the remaining 30% of deaths were due to medical co-morbid conditions. Overall survival was negatively impacted by increasing age (age > 60years), number of positive nodes, presence of perinodal spread, and stage of the disease. Recurrence-free survival was significantly reduced in those with the presence of peri-nodal spread and lympho-vascular space invasion. The incidence of lymph node metastasis was found to be higher in patients with age > 60years, increasing tumor size, presence of lympho-vascular space invasion and the number of lymph nodes removed. In carcinoma vulva, treatment should be individualized with multidisciplinary cooperation. In our series, we found that the stage of disease, nodal positivity, and nodal positivity with extra-capsular spread were significant prognostic factors impacting survival on analysis. Lymph nodal positivity was associated with increasing tumour size, presence of lympho-vascular invasion, and patient age.

Discordance between clinical and pathologic staging and the timeliness of care of non-small cell lung cancer patients diagnosed with operable tumors.

This study was performed to evaluate concordance between clinical and pathologic staging of non-small cell lung cancer (NSCLC) in our hospital network. We retrospectively reviewed records of 417 patients with NSCLC who received curative surgery and whose pathology was evaluated in our hospital between 2016 and 2021. Cytology, tissue pathology, and associated clinical, surgical, and imaging information were retrieved from hospital digital records. The cohort included 214 female and 203 male patients aged 20.6-85.8 years. Median times among staging computed tomography and surgery (105 days [interquartile range (IQR) 77.0-143.0]), positron emission tomography and surgery (78.5 days [IQR 56.0-109.0]), and endobronchial ultrasound-guided transbronchial needle aspiration and surgery (59 days [IQR 42-94]) indicated that Australian guidelines of <42 days between original referral and commencement of treatment were not being met in the majority of cases. Discordance between clinical TNM (cTNM) and pathologic TNM staging was 25.9%, including 18.4% cases that were clinically understaged and two patients with undetected stage IVA disease. cTNM understaging was significantly associated with time between the final staging investigation and surgery (p=.023), pleural (p<.05) and vessel (p<.05) invasion, and diagnosis of high-grade adenocarcinoma (p=.001). Discordance between clinical and pathologic staging of NSCLC is associated with tumor histopathologic characteristics and treatment delays. Although tumor factors that lead to discordant staging cannot be controlled, reduced time to surgery may have resulted in better outcomes for some patients in this potentially curable lung cancer cohort.

Impact of induction chemotherapy on Resectability in Locally advanced oral cavity Carcinomas

Purpose: We aim to assess resectability in patients with locally advanced oral cavity squamous cell carcinomas with induction chemotherapy (ICT). Methods: All stage III-IVB oral squamous cell carcinoma patients with borderline resectable (suspected R1) or unresectable disease (stage IVB, except internal carotid artery encasement or pterygoid plate or skull base involvement) recruited between January 2020 and August 2021 at a tertiary care hospital received 2-3 cycles of ICT (standard TPF regimen) followed by a surgical assessment. The primary aim was to evaluate the proportion of patients that became resectable by ICT. Results: Out of 40 patients, 21 were unresectable (stage IVB disease), and 19 were borderline resectable (stage IVA disease) with doubtful resection margins as per the multi-disciplinary discussion. After chemotherapy, 21 patients became resectable (13 out of 19; and 8 out of 21). Thus, resectability was achieved in 52.5% of patients (32.5% for stage IVA and 20% for stage IVB). The median overall survival (OS) in patients who underwent surgery was 20.5 months (95% CI: 16.95-28.25 months) versus 8.0 months (95% CI: 5.74-13.46 months) in patients who remained unresectable after induction chemotherapy (p=0.0001). Conclusions: In our study, induction chemotherapy leads to improved surgical resection rates with acceptable toxicities in a significant proportion of unresectable locally advanced oral cancers, with improved overall survival significantly.

Heterogeneity of outcomes of endometrial cancer patients included in prospective clinical trials

ObjectiveTo assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. MethodsThe National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. ResultsA total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%–81.7% for patients meeting GOG-249 inclusion criteria, 40.2%–81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%–75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. ConclusionsRecent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results.

Necitumumab plus gemcitabine and cisplatin in previously treated lung squamous cell carcinoma.

The efficacy and safety of the anti-EGFR antibody necitumumab combined with gemcitabine and cisplatin (N + GC) in the first-line treatment of advanced lung squamous cell carcinoma (LSCC) have been proven. However, the efficacy and safety of N + GC in the second line or later treatment remain unclear. Eleven patients who received N + GC for advanced-stage or recurrent LSCC were enrolled. We retrospectively assessed the patients' clinical characteristics and efficacy and safety of treatment. The median patient age was 73 years (range, 63-77 years). The cohort included nine(81.8%) men and two(18.2%) women. Two (18.2%) patients had postoperative recurrence, and one (9.1%), three (27.3%), one (9.1%), and four (36.4%) patients were diagnosed with stage IIIA, IIIB, IVA, and IVB disease, respectively. Concerning the best overall response, partial response was achieved in five (45.5%) patients, four (36.4%) patients displayed stable disease, and two (18.2%) patients were not evaluable. Median progression-free survival was 6.8 months (range, 1.4-10.3 months). The grade 3 or higher neutropenia, thrombocytopenia, and anemia occurred in six (54.5%), three (27.3%), and two (18.2%) patients, respectively. Additionally, grade 3 skin reaction, rash, lung infection, duodenal ulcer, and febrile neutropenia were observed in one (9.1%) patient each. Two (18.2%) patients required treatment interruption because of adverse events. N + GC displayed good efficacy in the second line or later treatment among patients with LSCC. This study suggested that N + GC is a useful option even after second-line treatment of advanced-stage or recurrent LSCC, although the management of adverse events is essential.

Time to completion of radiation treatment in locally advanced squamous cell carcinoma of the vulva and the impact on survival

ObjectiveTo assess whether radiation completion within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS). MethodsThe National Cancer Database from 2004 to 2017 was used to identify women ≥18 years old with stage II-IVA squamous cell vulvar cancer. We included women who received radiation alone (RT) or concurrent chemoradiation (CRT) for initial vulvar cancer treatment. Primary outcome was overall survival associated with time of delay in radiation completion. ResultsThere were 2378 women identified (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56–78), majority (88.35%) were white with advanced stage III or IVA (72.29%) disease. Median radiation dose was 5720 c-Gray (IQR 5040–6300). Radiation completion with delay ≥7 days resulted in reduction in survival compared to delay of <7 days (unadjusted HR 1.183 [95%CI: 1.066–1.313], p = 0.0016). When delays extended to ≥14 days compared to <14 days there was increased hazard of death (unadjusted HR: 1.263 [95%CI:1.126–1.416], p < 0.0001). Survival improved for patients with <7 versus ≥7 days delay whether treatment was with RT (median OS: 34.9 months versus 21.6 months, p < 0.01) or CRT (Median OS:58 months versus 41.3 months, p < 0.01). Stage IVA disease was associated with the greatest increase in hazard of death (HR 1.759 [95%CI 1.517–2.039], p < 0.0001) compared to stage II. ConclusionRadiation completion with <7 days delay is associated with improved overall survival, independent of concurrent chemotherapy. This suggest that strategies to minimize delays in radiation are crucial in locally advanced vulvar cancer.

Pretreatment hematological parameters as predictors of tumor granulocyte-colony-stimulating factor expression in patients of head-and-neck squamous cell carcinoma.

Tumor secreting granulocyte-colony-stimulating factor (G-CSF) and/or G-CSF therapy has been documented as a poor prognostic factor. Tumor G-CSF study is a relatively costly and sparsely available investigation. Therefore, this study was undertaken to predict tumor G-CSF score from pretreatment hematological parameters (PTHP) in patients of head-and-neck squamous cell carcinoma (HNSCC). This pilot study was performed after institutional ethics committee approval. Consecutive nonmetastatic HNSCC patients of oral cavity, oropharynx, hypopharynx, and larynx registered from February to December 2019 were analyzed. Patients whose PTHP and formalin-fixed-paraffin-embedded tissue were available, were included. PTHP (absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute lymphocyte count [ALC], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) done before any active oncology treatment, were noted. A semiquantitative tumor G-CSF score was calculated. Tumor G-CSF score and PTHP were correlated with clinicopathological factors. Statistical analysis was performed using SYSTAT version 12. Data of 47 eligible patients were analyzed. The median age at presentation was 60 years. The male-to-female ratio was 43:4. The most common head-and-neck subsite was oropharynx (31.92%), and majority of patients presented with Stage IVA disease (51.1%). Higher tumor G-CSF score was significantly associated with a higher T-stage (P = 0.013). Tumor G-CSF score was directly proportional to ANC, AMC, and ALC while it was inversely proportional to NLR and PLR. Regression equations to predict the tumor G-CSF score when PTHP are known, were determined. PTHP can predict the tumor G-CSF score which may guide G-CSF-directed therapy. Future studies with large number of patients are needed to elucidate its clinical use.