Hematological Parameters at Baseline: A Novel Prognostic Factor for Cervical Cancer Patients Undergoing Concurrent Chemoradiotherapy in South India.

Introduction In cervical cancer treatment, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin-globulin ratio (AGR) are being studied as potential prognostic markers for predicting the effectiveness of concurrent chemoradiotherapy (CCRT). This study aims to investigate the relationship between these biomarkers and survival outcomes in cervical cancer patients undergoing CCRT. Materials and methods This retrospective study was conducted at Amrita Institute of Medical Sciences between January 2016 and December 2019. It included patients at any stage who received definitive CCRT and were followed for at least two years post-treatment. Patients who had initial surgery and those lost to follow-up were excluded. Results The study included 123 patients with a median age of 68. Most patients had stage IIB (39%) and squamous cell carcinoma (76.4%). With a median follow-up of 56 months, the five-year overall survival (OS) was 66.8%, progression-free survival (PFS) was 94%, and recurrence-free survival (RFS) was 81.2%. AGR (p = 0.001), NLR (p = 0.0001), and PLR (p = 0.001) were found to be significantly associated with OS, NLR (p = 0.002) and AGR (p = 0.001) significantly affected RFS, while only PLR (p = 0.02) significantly affected PFS on univariate analysis. NLR significantly impacted OS (p = 0.003) and RFS (p = 0.03) on multivariate analysis. Conclusion The results of our study showed that increased NLR and elevated levels of albumin indicate a higher likelihood of mortality. Furthermore, a higher NLR was linked to an increased probability of recurrence in patients with cervical cancer who received primary treatment with CCRT. Therefore, the identification of predictive biomarkers could significantly improve the assessment of progression risk, aiding in the selection of the most suitable treatment and personalized therapy.

A longitudinal assessment of major mouthwashes used in alleviating pain and xerostomia among advanced nasopharyngeal carcinoma patients receiving chemoradiotherapy.

OBJECTIVE: This longitudinal study aimed to evaluate the overall efficacy of mouthwashes in oral mucositis pain and mucositis xerostomia in advanced nasopharyngeal carcinoma (NPC) patients undergoing concurrent chemoradiotherapy (CCRT) at different phases throughout treatment. METHODS: A longitudinal study enrolled 79 advanced NPC subjects receiving CCRT. The subjects were interviewed prospectively three times over 7 weeks for pain and xerostomia scores based on the various types of mouthwash used. The median pain score difference and median xerostomia score difference were utilised to determine mouthwash superiority. RESULTS: Participants completed three interviews, during which 480 instances of mouthwash use were observed throughout different phases of the treatment period. The results showed that the median pain scores between mouthwashes differed significantly, H-Stat(3) = 30.0, 25.7 and 26.0, respectively, with p < 0.001 for all three interviews. The pain score reductions of lidocaine mouthwash (median = 2, interquartile range (IQR) = 3, 2 and 2.75 over the three interviews, respectively) were significantly higher than those of benzydamine and sodium bicarbonate mouthwashes. There were no significant differences between the studied mouthwashes in their xerostomia score reductions. CONCLUSIONS: Lidocaine mouthwash was superior in managing oral mucositis pain at all phases throughout the entire chemoradiotherapy treatment for advanced NPC patients. There was insufficient evidence to determine the preferred mouthwash for treating oral mucositis xerostomia.

Accelerated Radiotherapy Alone Versus Chemoradiation in Locally Advanced Carcinoma Cervix: Long-Term Outcomes.

Introduction Chemoradiation (CRT) is the standard of care for the treatment of carcinoma cervix, more benefits of CRT are seen in the early stage as compared to a locally advanced stage. Altered fractionation such as accelerated radiotherapy (ART) in locally advanced carcinoma cervix has not been explored much. Here, we have reported the long-term outcome of ART in comparison to conventional CRT in locally advanced cervical cancer patients. Methods From September 2011 to January 2014, 191 patients with locally advanced squamous cell carcinoma of the uterine cervix, FIGO stage IIB - IIIB were included in this study. They were randomized into two arms: the CRT arm (95 patients) versus the ART arm (96 patients). During external beam radiotherapy (EBRT), the patients in the CRT arm received conventional radiotherapy 50 Gy/25 fractions, 2 Gy/fraction, 5 fractions/week with cisplatin 40 mg/m2/week while patients in the ART arm received 50 Gy/25 fractions, 2 Gy/fraction, 6 fractions per week (Monday to Saturday) radiation alone. This was followed by three insertions of 6.5 Gy per fraction of high dose rate (HDR) brachytherapy at one-week intervals in both arms to keep the total treatment time 50 days in the CRT arm versus 45 days in the ART arm. Results The median follow-up of the study population was 57 months (range: 4-108 months). The patients with no residual disease (NRD) after EBRT and complete response (CR) at first follow-up were statistically less in the ART arm as compared to the CRT arm (30.2% versus 53.7% and 42.7% versus 63.2%; p = 0.006 and p = 0.024, respectively). However, there was no statistical difference in response at six months. High-grade acute toxicities hematological (9.5%) and gastrointestinal (15.8%) were more prevalent in the CRT arm in comparison to the ART arm, with no statistical significance (p>0.05) and Grade 1/2 genitourinary toxicity was significantly higher in the CRT arm. Late toxicities in both groups were equivalent. Recurrence, distant type of recurrence, and time to recurrence were similar in both groups. Five-year rates of overall survival (OS) and disease-free survival (DFS) were 51.2% versus 37.2% (p = 0.087) and 57.1% versus 46.3% (p = 0.223) in the CRT arm versus ART arm, respectively. Conclusion ART is a compelling alternative to concurrent chemoradiotherapy for locally advanced cervical cancer, particularly in patients with significant comorbidities, elderly women, and those in higher stages where concurrent chemotherapy's efficacy diminishes. It should be strongly considered when chemotherapy is contraindicated.

Dramatic Radiographic Response of Pelvis-Filling Locally Advanced Cervical Cancer Treated With Radiation and Chemotherapy.

Locally advanced cervical cancers are often treated with palliative intent due to concerns that the tumor is too far advanced or too large to be treated curatively. Also, patients greater than 65 years of age with cervical cancer are sometimes regarded as being too old or too frail to be cured with combined radiation and chemotherapy. These patients are often treated with radiation alone or with palliative therapy. Understanding the treatment modalities for cervical cancer is essential, as they can be complex and unique to each patient's specific diagnosis. This case report aims to describe the dramatic response to treatment with combined radiation and chemotherapy for a patient greater than 65 years of age with pelvis-filling cervical cancer with right-sided hydronephrosis. After a five-week course of concurrent chemoradiation, the cervical mass radiographically completely disappeared, with no evidence of disease noted on pelvic MRI.

Correlation of maintenance chemotherapy and improved survival in patients with locally advanced unresectable pancreatic head adenocarcinoma receiving neoadjuvant chemotherapy and concurrent chemoradiotherapy.

To assess the efficacy of maintenance chemotherapy in the management of unresectable locally advanced pancreatic head adenocarcinoma (PHA) cancer after neoadjuvant chemotherapy and concurrent chemoradiation therapy (CCRT). This study, a large-scale head-to-head propensity score matching (PSM) cohort study, employed real-world data. PSM was used to evaluate the impact of maintenance chemotherapy on overall survival and cancer-specific survival in patients with unresectable locally advanced PHA who underwent neoadjuvant chemotherapy and CCRT. A total of 148 patients with locally advanced pancreatic head adenocarcinoma were included in the study after PSM. These patients were equally divided into two groups, those receiving maintenance chemotherapy and those who did not. Confounding factors were balanced between the groups. The adjusted hazard ratios for all-cause mortality and cancer-specific mortality were 0.56 (95% CI: 0.40-0.77; P = 0.0005) and 0.56 (95% CI: 0.40-0.78; P = 0.0007), respectively, in patients receiving maintenance chemotherapy compared to those who did not. Our large-scale, real-world study demonstrates that maintenance chemotherapy may enhance survival outcomes for patients with unresectable locally advanced pancreatic head adenocarcinoma who underwent neoadjuvant chemotherapy and concurrent chemoradiation therapy.

Risk Factor Analysis of Morbidity and 90-Day Mortality of Curative Resection in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer after Induction Concurrent Chemoradiation Therapy.

Background: Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA-N2 non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA-N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression. Results: A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p<0.01) were independent predictors of mortality in the multivariable analysis. Conclusion: In conclusion, the surgical outcomes following nCCRT are less favorable for individuals aged over 70 years or those undergoing pneumonectomy. Special attention is warranted for these patients due to their heightened risks of respiratory complications. In high-risk patients, such as elderly patients with decreased lung function, alternative treatment options like definitive CCRT should be considered instead of surgical resection.

Utilization and Impact of a Radiation Nursing Clinic to Address Acute Care Needs for Patients with Gynecologic Cancers.

BACKGROUND: The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre's acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT). METHODS: This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher's exact test were used for comparisons of continuous and categorical variables, respectively. RESULTS: RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre. CONCLUSIONS: The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed.

Long-Term Survival After Definitive Concurrent Chemoradiation Therapy for Synchronous Small Cell Neuroendocrine Carcinoma of the Urinary Bladder and Adenocarcinoma of the Prostate: A Case Report.

Available reports of synchronous prostate and bladder cancer have exclusively described radical cystoprostatectomy with or without perioperative chemotherapy as the treatment of choice. There are no reports of curative intent or definitive chemoradiation therapy for synchronous primary bladder and primary prostate cancers. Small cell carcinoma of the bladder is a rare and aggressive tumor. We present the first case of synchronous mixed small cell carcinoma and urothelial carcinoma of the urinary bladder and adenocarcinoma of the prostate in a 70-year-old male who attained long-term survival after curative intent and definitive concurrent chemoradiotherapy with minimal acute and late toxicities. The patient remained alive and disease-free at 41 months post-treatment and achieved excellent functional outcomes with organ preservation. Definitive chemoradiation therapy offers a safe and effective, curative-intent organ preservation treatment for localized synchronous prostate and bladder cancers.

Urinary, Gastrointestinal, and Sexual Dysfunctions after Chemotherapy, Radiotherapy, Radical Surgery or Multimodal Treatment in Women with Locally Advanced Cervical Cancer: A Multicenter Retrospective Study.

BACKGROUND: Different strategies have been proposed for the treatment of locally advanced cervical cancer (LACC), with different impacts on patient's quality of life (QoL). This study aimed to analyze urinary, bowel, and sexual dysfunctions in a series of LACC patients who underwent chemotherapy, radiotherapy, radical surgery, or a combination of these treatments. METHODS: Patients with LACC who underwent neoadjuvant radio-chemotherapy (NART/CT; n = 35), neoadjuvant chemotherapy (NACT; n = 17), exclusive radio-chemotherapy (ERT/CT; n = 28), or upfront surgery (UPS; n = 10) from November 2010 to September 2019 were identified from five oncological referral centers. A customized questionnaire was used for the valuation of urinary, gastrointestinal, and sexual dysfunctions. RESULTS: A total of 90 patients were included. Increased urinary frequency (>8 times/day) was higher in ERT/CT compared with NACT/RT (57.1% vs. 28.6%; p = 0.02) and NACT (57.1% vs. 17.6%; p = 0.01). The use of sanitary pads for urinary leakage was higher in ERT/CT compared with NACT/RT (42.9% vs. 14.3%; p = 0.01) and NACT (42.9% vs. 11.8%; p = 0.03). The rate of reduced evacuations (<3 times a week) was less in UPS compared with NACT/RT (50% vs. 97.1%; p < 0.01), NACT (50% vs. 88.2, p < 0.01), and ERT/CT (50% vs. 96.4%; p < 0.01). A total of 52 women were not sexually active after therapy, and pain was the principal reason for the avoidance of sexual activity. CONCLUSIONS: The rate and severity of urinary, gastrointestinal, and sexual dysfunction were similar in the four groups of treatment. Nevertheless, ERT/CT was associated with worse sexual and urinary outcomes.

Quantification of diffuse parenchymal lung disease in non-small cell lung cancer patients with definitive concurrent chemoradiation therapy for predicting radiation pneumonitis.

BACKGROUND: We sought to quantify diffuse parenchymal lung disease (DPLD) extent using quantitative computed tomography (CT) analysis and to investigate its association with radiation pneumonitis (RP) development in non-small cell lung cancer (NSCLC) patients receiving definitive concurrent chemoradiation therapy (CCRT). METHODS: A total of 82 NSCLC patients undergoing definitive CCRT were included in this prospective cohort study. Pretreatment CT scans were analyzed using quantitative CT analysis software. Low-attenuation area (LAA) features based on lung density and texture features reflecting interstitial lung disease (ILD) were extracted from the whole lung. Clinical and dosimetric factors were also evaluated. RP development was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors for grade ≥3 (≥GR3) RP. RESULTS: RP was identified in 68 patients (73.9%), with nine patients (10.9%) experiencing ≥GR3 RP. Univariable logistic regression analysis identified excess kurtosis and high-attenuation area (HAA)_volume (cc) as significantly associated with ≥GR3 RP. Multivariable logistic regression analysis showed that the combined use of imaging features and clinical factors (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and CHEMO regimen) demonstrated the best performance (area under the receiver operating characteristic curve = 0.924) in predicting ≥GR3 RP. CONCLUSION: Quantified imaging features of DPLD obtained from pretreatment CT scans would predict the occurrence of RP in NSCLC patients undergoing definitive CCRT. Combining imaging features with clinical factors could improve the accuracy of the predictive model for severe RP.

Ten years survival results of randomized study comparing weekly vs. triweekly cisplatin with concurrent radiation in locally advanced carcinoma cervix.

Background: The current standard of treatment for locally advanced cervical cancer is concurrent chemo-radiation with improved overall survival (OS) by 6% with manageable toxicities. The cisplatin 40 mg/m2 given weekly is the widely practiced regimen for 4-6 cycles concurrently with irradiation. Materials and methods: Two hundred and twelve patients with histologically proven squamous cell carcinoma of cervix with stages IIB to IIIB were enrolled between 2007-2011. External beam radiation dose of 45 Gy in 25 fractions was delivered over 5 weeks. Brachytherapy was delivered by manual afterloading cesium-137 (Cs137) low dose brachytherapy (LDR) using modified Fletcher suit intracavitary applicators to a total dose of 30 Gy to Point A or interstitial template to dose of 21 Gy/3 fractions with remote afterloading iridium-192 (Ir192) high dose brachytherapy (HDR). Patients were randomized to arm A receiving 40 mg/m2 of concurrent cisplatin weekly and arm B receiving 100 mg/m2 of concurrent cisplatin triweekly. Results: One hundred and nine patients were randomized to weekly cisplatin and one hundred and three patients to triweekly cisplatin at the end of recruitment. At ten years, the OS was higher in the weekly arm (79.8%) compared to triweekly arm (70.9%). Disease free survival (DFS) was almost equal (76.1% and 73.8%) in the weekly and three-weekly arms. There is definite significance in overall DFS with patients receiving the cumulative cisplatin doses of more than 250 mg (p = 0.028). The patients with more than 45 years of age had better overall survival (OS) (79%) with statistical significance 31 (p = 0.020). Conclusion: Both cisplatin based triweekly and weekly concurrent chemotherapy are equally effective in terms of OS and DFS.

Management and outcome of locally advanced oral squamous cell carcinoma.

Management of locally advanced OSCC is multimodal. No single therapy has been proved to be efficacious. However there is a trend towards surgical intervention in operable disease. In this review we appraise the various therapies used for the management of locally advanced OSCC. We review the literature with regards to the various treatment options for locally advanced OSCC. We categorically divided the manuscript into resectable, unresectable and technically unresectable disease. Surgery is the ideal treatment modality for resectable disease. For unresectable disease concurrent chemoradiation appears to improve survival compared to radiotherapy alone. Induction therapy might downstage tumors in the unresectable category. Targeted and Immunotherapy is reserved for recurrent, metastatic or platinum refractory OSCC. Management of locally advanced OSCC is multimodal with surgery playing the primary role. In the event where the tumor is in operable concurrent chemoradiotherapy is regarded as the best treatment modality. Induction chemotherapy currently cannot be recommended for resectable or even unresectable oral squamous cell carcinomas. However for technically unresectable disease it might play a role in improving respectability but it depends on the response of the tumor. Targeted therapy and immunotherapy is currently used for recurrent, metastatic and/or platinum refractory Head and Neck cancers. Currently it is not recommended for initial management of locally advanced disease.

Cardiac Dose Predicts the Response to Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

Definitive concurrent chemoradiation (CCRT) is the standard treatment for cervical esophageal cancer and non-surgical candidates. Initial treatment response affects survival; however, few validated markers are available for prediction. This study evaluated the clinical variables and chemoradiation parameters associated with treatment response. Between May 2010 and April 2016, 86 completed CCRT patients' clinical, dosimetric, and laboratory data at baseline and during treatment were collected. Cox regression analysis assessed the risk factors for overall survival (OS). A receiver operating characteristic curve with Youden's index was chosen to obtain the optimal cut-off value of each parameter. Treatment response was defined per Response Evaluation Criteria in Solid Tumors v.1.1 at the first post-CCRT computed tomography scan. Responders had complete and partial responses; non-responders had stable and progressive diseases. Logistic regression (LR) was used to evaluate the variables associated with responders. The Cox regression model confirmed the presence of responders (n = 50) vs. non-responders (n = 36) with a significant difference in OS. In multivariate LR, cardiac dose-volume received ≥10 Gy; the baseline hemoglobin level, highest neutrophil to lymphocyte ratio during CCRT, and cumulative cisplatin dose were significantly associated with the responders. The initial clinical treatment response significantly determines disease outcome. Cardiac irradiation may affect the treatment response.

Accelerated loss of lean body mass in head and neck cancer patients during cisplatin-based chemoradiation.

BACKGROUND: This study investigated changes in body weight, lean body mass (LBM), fat mass (FM), muscle strength and functional performance during radiation treatment in head and neck cancer (HNSCC) patients. Secondly, it investigated the impact of cisplatin-based chemoradiation (CCRT) on LBM loss compared with radiation alone. METHODS: 48 patients (all tumor sites) received either 6 weeks of radiation alone (n = 16) with 66-68 Gy in 33-34 Fx, 5-6 Fx/week or CCRT, adding weekly cisplatin or carboplatin (n = 32). LBM and FM was evaluated using Dual-energy X-ray Absorptiometry bi-weekly from pre- to two weeks post-treatment. Maximal muscle strength (knee extension, leg - and chest press) and functional performance (stair climb, chair rise, and arm curl) were assessed pre- and post-treatment. RESULTS: Body weight and LBM had declined significantly already week 2 into treatment and declined significantly further through week 4 and 6 before leveling off after week 6. Bi-weekly, from treatment start to week 2, 2-4, and 4-6, LBM declined 1.2 ± 0.4 kg (p = .002; 95% CI: 0.4;2.0), 2.0 ± 0.4 kg (p < .0001; 1.2;2.8) and 1.4 ± 0.4 kg (p = .001; 0.6;2.2). With a two-week delay, FM declined significantly from week 2-8. All measures of muscle strength declined significantly from pre- to post-treatment. Functional performance was unchanged. LBM loss from pre- to post-treatment was significantly associated with impaired muscle strength (R2 = 0.3-0.5). CCRT patients lost 3.1 ± 0.8 kg of LBM (p = .0001; 1.5;4.7) more from pre- to post-treatment compared with patients receiving radiation alone. Analyses adjusting for nimorazole, tumor stage, baseline BMI, mean radiation dose to constrictor muscles and oral cavity confirmed this. CONCLUSION: Accelerated and substantial LBM loss was already initiated within the first two weeks of treatment - before the onset of radiation-induced mucositis. LBM loss was associated with muscle strength impairment. Patients receiving CCRT experienced significantly larger LBM loss than patients receiving radiation alone. Registered on clinincaltrials.gov (Identifier: NCT05890859).

Profile Characterization of Biogenic Amines in Glioblastoma Patients Undergoing Standard-of-Care Treatment.

INTRODUCTION: Biogenic amines play important roles throughout cellular metabolism. This study explores a role of biogenic amines in glioblastoma pathogenesis. Here, we characterize the plasma levels of biogenic amines in glioblastoma patients undergoing standard-of-care treatment. METHODS: We examined 138 plasma samples from 36 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma at multiple stages of treatment. Untargeted gas chromatography-time of flight mass spectrometry (GC-TOF MS) was used to measure metabolite levels. Machine learning approaches were then used to develop a predictive tool based on these datasets. RESULTS: Surgery was associated with increased levels of 12 metabolites and decreased levels of 11 metabolites. Chemoradiation was associated with increased levels of three metabolites and decreased levels of three other metabolites. Ensemble learning models, specifically random forest (RF) and AdaBoost (AB), accurately classified treatment phases with high accuracy (RF: 0.81 ± 0.04, AB: 0.78 ± 0.05). The metabolites sorbitol and N-methylisoleucine were identified as important predictive features and confirmed via SHAP. CONCLUSION: To our knowledge, this is the first study to describe plasma biogenic amine signatures throughout the treatment of patients with glioblastoma. A larger study is needed to confirm these results with hopes of developing a diagnostic algorithm.

Concurrent Radiation and Targeted Therapy for Papillary Craniopharyngioma: A Case Report.

Craniopharyngiomas are rare epithelial malformations in the sellar or suprasellar regions of the craniopharyngeal ducts. Complete surgical resection is difficult due to the location of the base of the skull and the risk of injury to vital neurological structures. Fractionated radiation is effective in controlling residual tumors, but craniopharyngiomas can progress during treatment. The papillary subtype is driven by BRAF V600E mutations. Treatment with BRAF and MEK inhibitors alone has a response rate of 90% but a median progression-free survival of only 12 months. A 57-year-old female presented in May 2017 with complaints of headaches and blurriness in her right eye. Brain MRI demonstrated a 2 cm suprasellar mass engulfing the right optic nerve and optic chiasm. The patient underwent a transsphenoidal hypophysectomy with pathology consistent with a benign pituitary adenoma. Follow-up imaging in August, however, showed recurrence, and a re-resection was performed which surprisingly demonstrated papillary craniopharyngioma. Due to subtotal resection, the patient elected to proceed with intensity-modulated radiation therapy (IMRT) to the tumor bed in April of 2018 with an intended dose of 5400 cGy. After treatment with 2160 cGy in 12 fractions, the patient experienced visual deterioration and progression of the cystic tumor. The patient underwent another debulking procedure but due to rapid recurrence, an endoscopic transsphenoidal fenestration was performed. On postoperative imaging, a cystic mass was still engulfing the right optic nerve and chiasm. Due to the extended break and limited radiation tolerance of the optic chiasm, we elected to re-treat the tumor with an additional 3780 cGy IMRT in conjunction with one cycle of Taflinar and Mekinist, which was completed in August 2018. The cumulative dose to the optic chiasm was 5940 cGy.The patient had an excellent clinical response to treatment with the improvement of vision in her right eye. A brain MRI on 3/29/2019 demonstrated no residual craniopharyngioma. Four-year follow-on CT scan showed no evidence of tumor recurrence. The patient had preservation of vision and did not suffer any late neurological toxicity or new endocrine deficiency. Surgical resection and radiation were ineffective at treating our patient's craniopharyngioma due to rapid cystic progression. This is the first case report in the literature detailing concurrent radiation therapy with BRAF and MEK inhibitors for papillary craniopharyngioma. Despite a suboptimal dose of radiation, our patient had no tumor recurrence and no late toxicity four years after treatment. This represents a potentially novel treatment strategy in this challenging entity.

Pneumonitis After Concurrent Chemoradiation and Immune Checkpoint Inhibition in Patients with Locally Advanced Non-small Cell Lung Cancer.

AIMS: Pneumonitis is a common and potentially deadly complication of combined chemoradiation and immune checkpoint inhibition (CRT-ICI) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). In this study we sought to identify the risk factors for pneumonitis with CRT-ICI therapy in LA-NSCLC cases and determine its impact on survival. MATERIALS AND METHODS: We conducted a retrospective chart review of 140 patients with LA-NSCLC who underwent curative-intent CRT-ICI with durvalumab between 2018 and 2021. Pneumonitis was diagnosed by a multidisciplinary team of clinical experts. We used multivariable cause-specific hazard models to identify risk factors associated with grade ≥2 pneumonitis. We constructed multivariable Cox proportional hazard models to investigate the impact of pneumonitis on all-cause mortality. RESULTS: The median age of the cohort was 67 years; most patients were current or former smokers (86%). The cumulative incidence of grade ≥2 pneumonitis was 23%. Among survivors, 25/28 patients had persistent parenchymal scarring. In multivariable analyses, the mean lung dose (hazard ratio 1.14 per Gy, 95% confidence interval 1.03-1.25) and interstitial lung disease (hazard ratio 3.8, 95% confidence interval 1.3-11.0) increased the risk for pneumonitis. In adjusted models, grade ≥2 pneumonitis (hazard ratio 2.5, 95% confidence interval 1.0-6.2, P = 0.049) and high-grade (≥3) pneumonitis (hazard ratio 8.3, 95% confidence interval 3.0-23.0, P < 0.001) were associated with higher all-cause mortality. CONCLUSIONS: Risk factors for pneumonitis in LA-NSCLC patients undergoing CRT-ICI include the mean radiation dose to the lung and pre-treatment interstitial lung disease. Although most cases are not fatal, pneumonitis in this setting is associated with markedly increased mortality.

Concurrent chemotherapy with partial breast irradiation in triple negative breast cancer patients may improve disease control compared with sequential therapy.

Purpose: To report outcomes on a subset of patients with triple negative breast cancer (TNBC) treated on prospective trials with post-lumpectomy partial breast irradiation and concurrent chemotherapy (PBICC) and compare them to a retrospectively assessed similar cohort treated with whole breast irradiation after adjuvant chemotherapy (WBIaC). Methods and materials: Women with T1-2, N0-1 invasive breast cancer with ≥ 2mm lumpectomy margins were offered therapy on one of two PBICC trials. PBI consisted of 40.5 Gy in 15 daily 2.7 Gy fractions delivered concurrently with the first 2 cycles of adjuvant chemotherapy. The comparison cohort received WBI to a median dose of 60.7 Gy, (including boost, range 42.5 - 66 Gy), after completion of non-concurrent, adjuvant chemotherapy. We evaluated disease-free survival (DFS), and local/loco-regional/distant recurrence-free survival (RFS). We compared survival rates using Kaplan-Meier curves and log-rank test of statistical significance. Results: Nineteen patients with TNBC were treated with PBICC on prospective protocol, and 49 received WBIaC. At a median follow-up of 35.5 months (range 4.8-71.9), we observed no deaths in the PBICC cohort and 2 deaths in the WBIaC cohort (one from disease recurrence). With a median time of 23.4 (range 4.8 to 47) months, there were 7 recurrences (1 nodal, 4 local, 4 distant), all in the WBIaC group. At 5 years, there was a trend towards increased local RFS (100% vs. 85.4%, p=0.17) and loco-regional RFS (100% vs. 83.5, p=0.13) favoring the PBICC cohort. There was no significant difference in distant RFS between the two groups (100% vs. 94.4%, p=0.36). Five-year DFS was 100% with PBICC vs.78.9% (95% CI: 63.2 to 94.6%, p=0.08) with WBIaC. Conclusion: This study suggests that PBICC may offer similar and possibly better outcomes in patients with TNBC compared to a retrospective cohort treated with WBIaC. This observation is hypothesis-generating for prospective trials.

A Comparison of the Toxicities in Patients With Locally Advanced Head and Neck Cancers Treated With Concomitant Boost Radiotherapy Versus Conventional Chemoradiation.

PURPOSE: To compare the objective and patient-reported toxicities of concomitant boost radiotherapy (CBRT) and concurrent chemoradiation (CRT) in patients with locally advanced head and neck cancers. METHODS AND MATERIAL: In this prospective study, 46 patients with histologically proven stage III-IVA head and neck cancer were randomly assigned to receive either concurrent chemoradiation to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (40 mg/m2 IV weekly; control arm) or accelerated radiotherapy with concomitant boost radiotherapy (study arm) to a dose of 67.5 Gy in 40 fractions in five weeks. Acute toxicity was evaluated using RTOG toxicity criteria. The assessment was done weekly after initiation of treatment, at the first follow-up (six weeks), and at three months. The four main patient-reported symptoms of pain, hoarseness of voice, dryness of mouth, and loss of taste were also compared between the two groups to assess patient quality of life during treatment. RESULTS: The mean treatment duration was 37 days in the CBRT arm and 49 days in the CRT arm. Treatment-related interruptions were less in the study group,17.3% in the study, and 27.2% in the control with insignificant P-value. Grade III laryngeal toxicity was significantly higher in the study group (P=0.029). Other acute grade I-III toxicities (pharyngeal, skin, mucositis, and salivary) were comparable in both CRT and CBRT arms. Grade IV toxicities were seen only in the CBRT arm but were resolved at the first follow-up. Haematological toxicities and renal toxicities were significantly higher in the CRT arm, with significant P-values of 0.0004 and 0.018, respectively. CONCLUSION: In patients with locally advanced head and neck cancer, concomitant boost radiotherapy is well tolerated with acceptable local toxicity and minimal systemic toxicity as compared to conventional chemoradiation. It is a feasible option for patients with locally advanced head and neck cancer not fit for concurrent chemoradiation.

Comparison of Oncologic Outcomes between Radical Hysterectomy and Primary Concurrent Chemoradiotherapy in Women with Bulky IB and IIA Cervical Cancer under Risk Stratification.

PURPOSE: To stratify patients according to tumor marker and histology and compare the survival outcome between radical hysterectomy (RH) and primary concurrent chemoradiotherapy (CCRT) in bulky IB and IIA cervical cancer. METHODS: A total of 442 patients with cervical cancer were enrolled in the Chang Gung Research Database from January 2002 to December 2017. Patients with squamous cell carcinoma (SCC) and carcinoembryonic antigen (CEA) ≥10 ng/mL, adenocarcinoma (AC), or adenosquamous carcinoma (ASC) were stratified into the high-risk (HR) group. The others were classified into the low-risk (LR) group. We compared oncology outcomes between RH and CCRT in each group. RESULTS: In the LR group, 5-year overall survival (OS) and recurrence-free survival (RFS) were 85.9% vs. 85.4% (p = 0.315) and 83.6% vs. 82.5% (p = 0.558) in women treated with RH (n = 99) vs. CCRT (n = 179), respectively. In the HR group, the 5-year OS and RFS were 83.2% vs. 73.3% (p = 0.164) and 75.2% vs. 59.6% (p < 0.036) in patients treated with RH (n = 128) vs. CCRT (n = 36), respectively. Regarding recurrence, locoregional recurrence (LRR) (8.1% vs. 8.6%, p = 0.812) and distant metastases (DM) (17.8% vs. 21%, p = 0.609) were similar between RH and CCRT in the LR group. However, lower LRR (11.6% vs. 26.3%, p = 0.023) but equivalent DM (17.8% vs. 21%, p = 0.609) were found for women undergoing RH compared with CCRT in the HR group. CONCLUSIONS: There were similar survival and recurrence rates between both treatment modalities in low-risk patients. Meanwhile, primary surgery with or without adjuvant radiation provides better RFS and local control in women with high-risk features. Further prospective studies are needed to confirm these findings.