Concurrent Chemo Research Articles

Survival and toxicity outcomes of induction chemotherapy followed by concurrent chemoradiotherapy compared with concurrent chemoradiotherapy alone in inoperable stage III and IVA/B head and neck cancer

Concurrent chemoradiotherapy with or without induction chemotherapy is widely practiced in inoperable stage III and IVA/B head and neck cancer. The aim of this study was to investigate the survival and toxicity outcomes of induction chemotherapy combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in inoperable stage III and IVA/B head and neck cancer patients. From June 2018 to July 2020, 86 patients participated in a quasi-experimental study. Patients were purposively assigned to one of the two arms (arm A or arm B). Arm A got induction chemotherapy and concurrent chemo- radiotherapy, while arm B got only concurrent chemoradiotherapy. According to our findings, the 2-year progression-free survival rate in arm A was 48.8% vs 37.2 % in arm B (p-value=0.042), and the 2-year overall survival rate in arm A was 65.1 % versus 60.5 % in arm B (p-value= 0.416). There were no statistically significant variations in treatment-related toxicities between the two groups (p-value > 0.05). In conclusion, inoperable stage III and IVA/B head and neck cancer patients who got induction chemotherapy plus concurrent chemotherapy had a better progression-free survival rate than those who received concur- rent chemoradiotherapy alone. BSMMU J 2021; 14(4): 144-147

A PROSPECTIVE COMPARATIVE STUDY BETWEEN CONCURRENT CHEMO RADIOTHERAPY WITH CISPLATIN AND ETOPOSIDE VERSUS PACLITAXEL AND CARBOPLATIN IN LOCALLY ADVANCED NON SMALL CELL LUNG CARCINOMA

Background-The current standard of treatment for unresectable locally advanced Non-small cell lung carcinoma is radiation with concurrent platinum based doublet chemotherapy. But there remains considerable debate over the optimal concurrent regimen , with some advocating Cisplatin-Etoposide , others prefer carboplatin-paclitaxel as an equally effective and better tolerable concurrent regimen.. With this background, our study was aimed at comparing loco-regional control and toxicity prole between these two regimens. Material And Methods- Locally advanced non-metastatic Non-small cell lung carcinoma patients were randomized in two groups- study group received External beam radiotherapy(60Gy/30 fractions/6 weeks) in conventional fractionation along with concurrent weekly chemotherapy with Inj.paclitaxel (45 mg/m2 ) and Inj. Carboplatin (AUC2 ) and control group received same radiotherapy dose with concurrent Inj.cisplatin (50mg/m2) Day 1,8,29,36 and Inj.Etoposide (50 mg/m2) Day 1-5 and Day 29-33. After treatment completion , Locoregional Tumor response was assessed . Patients were evaluated weekly for acute toxicity during radiation therapy, then once at 6-8 weeks after completion of treatment and thereafter every three months for at least 6 months. Results- Overall treatment Response in Study Arm was higher than control arm (73% vs 70%). Complete response rate was also higher in study arm (40% vs 30%) though these differences were not statistically signicant [p value 0.701]. Although statistically not signicant ,Grade III haematological toxicity was less (3% vs 6%) in study arm .Other toxicity proles including acute lung, esophageal and skin toxicities are comparable in both the arms of the study. Conclusion- Concurrent chemo- radiotherapy with cisplatin -etoposide versus paclitaxel -carboplatin in locally advanced NSCLC are comparable in terms of loco-regional control and acute toxicity.

Pre-treatment hematological parameters as a cost effective predictive marker for response to concurrent chemo radiation in locally advanced cervical cancer

IntroductionLocally advanced cervical cancer is still a major cause of mortality in developing countries. Recently, personalized medicine has changed the treatment paradigm for many solid cancers but no robust biomarkers has yet been validated for predicting response to chemo radiation in cervical cancer patients. AimTo assess the role of hematological parameters as a cost-effective predictive marker of response to concurrent chemo radiation in cervical cancer patients. Materials and MethodThis is a retrospective analysis of 90 cervical cancer patients treated with concurrent chemo radiation in a tertiary cancer center. Clinical details of the patients were extracted from the case records. For end point evaluation, the pre-treatment levels of hemoglobin, neutrophil, lymphocyte, platelet, platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) were compared and statistically analyzed between responders and non-responders. The optimal cutoff values of hematological parameters were estimated by the receiver operating characteristics (ROC) curve. ResultOut of 90 patients, 60 (66.66%) were complete responders and remaining 30 (33.33%) were non-responders. The mean value of platelet, NLR, and PLR was significantly higher in the non-responder group. ROC curve analysis showed the optimal cut-off value of pre-treatment Hb, PLT, NLR and PLR to be 11 gm/dl, 3, 177 × 109/L, and 70 respectively. ConclusionOur study suggests that simple hematological markers like NLR, PLT count and PLR could be used as a cost effective pretreatment predictive marker for response to chemo radiation in cervical cancer patients.

Examining the Benefits of Digitally Selectable Meals Called "À La Carte Digital-Select" in Cancer Chemotherapy Patients.

We explored the benefits of a digitized bedside terminal with a touchscreen for selectable hospital meals called “à la carte digital-select” in cancer chemotherapy patients. The subjects used “à la carte digital-select” for 35 days, from November to December 2015. On average, 253 (between 196 and 288) patients accessed this system per day, and 40 patients used it daily (15.9%). Subjects included 75 patients (cancer chemotherapy: chem-digital-select patients, female: 47) and 12 patients (concurrent chemo radiotherapy: CRT-digital-select patients, female: 6) with a repeat rate of 87% (65) and 100% (12). The average length of hospital stay in chem-digital-select patients was 6 days (1-35), the average number of days using “à la carte digital-select” was 3 days (1-24); a correlation was observed between these factors (r = .80; P < .01). The eating rate of chemotherapy patients and CRT-digital-select patients was high (81%, 81%), and no differences were observed between the rate in the cisplatin group (80%) with 28 patients, the non-cisplatin group (81%) with 47 patients, CRT-digital-select patients (81%) with 12 patients (P = .59; ANOVA). Registered dietitians provided no nutritional intervention in any of the cases. We found that “à la carte digital-select” can contribute to supporting cancer chemotherapy and the dietary needs of cancer patients undergoing chemotherapy.

Correlation of Hematological Toxicity with the Bone Marrow Radiation Dose and Volume during Concurrent Chemo Radiation in Patients with Cervical Cancer

Aims &amp; Objective: Hematological toxicity is common in patients with cervical cancer treated with concurrent chemo radiotherapy (CT-RT), so the purpose is to assess this hematological toxicity and correlate the toxicity with the dose and volume of bone marrow included in the field of radiation. Materials &amp; Methods: Twenty five patients with histologically proven cervical cancer attending to our Cancer centre from July 2018-August 2019 were the subjects of this study. Patients were treated on 6 MV linear accelerator with a radical intent with concurrent chemotherapy using cisplatin 50 mg weekly. The planning CT was done for all the patients before the treatment and contouring of the pelvic bone marrow apart from other organs at risk was done. Hematological toxicity was assessed using RTOG common toxicity criteria weekly during and at 2 weeks after the completion of the treatment. Results: A total of 25 patients on CT-RT treatment were assessed. Sixteen patients were in locally advanced stage. The variation in HB, TLC, Platelets, and ANC counts from the baseline to 2 weeks after chemo radiotherapy were assessed. Grade II anemia was observed in 12 and Grade III in 2 patients. There were no toxicity as far as WBC and platelets were considered. There was also no correlation between the volume of bone marrow included in the field of irradiation and appearance of anemia. Conclusion: CT-RT for cervical cancer is safe and is associated with minimal hematological toxicity in the form of anemia. The toxicity is same for different volumes of bone marrow included in the field of irradiation with both 3DCRT as well as IMRT technique. The toxicity observed is probably contributed by Cisplatin.

Dose-Escalated Accelerated Hypofractionation for Patients With a Newly Diagnosed Glioblastoma: A Pooled International Study

The standard of care (SOC) for elderly or frail glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy. However, this regimen has a lower BED compared to the Stupp regimen, 60 Gy in 30 fractions. We hypothesize that dose escalated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to standard of care.Elderly GBM patients treated with 52.5 Gy in 15 fractions were pooled from 2 phase II studies, 1 phase 1 and a prospective observation study. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Univariate and multivariate analyses were performed.Sixty-two newly diagnosed patients were eligible for this analysis. Median follow-up was 10 months. The median OS and PFS was 10.3 and 6.7 months, respectively. Patients with KPS ≥ 70 and < 70 had a median OS of 15.3 and 9.5 months. No survival difference was seen between unmethylated and methylated patients with a median OS of 10.2 and 10.3 months, respectively. Univariate analysis demonstrated younger age (P = 0.018) and concurrent chemo (P < 0.001) were associated with improved OS and gross total resection (P = 0.010), smaller PTV volume (P = 0.008) and concurrent chemo (P = 0.015) associated with improved PFS. Multivariate analysis demonstrated concurrent chemo to be an independent prognostic factor. Grade 3 or higher neurologic toxicity was seen in 2 patients (3.2%).This is the first pooled, prospective analysis of elderly/frail GBM patients treated with dose-escalated hypofractionated radiation. Treatment was well tolerated and demonstrated excellent OS and PFS, exceeding that from prior elderly trials (Roa; 6.5 months [poor KPS]/Perry; 9.3 months [good KPS]). This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. Future prospective trials are needed to validate these results.

Prospective Validation of the Magnetic Resonance Tumor Regression Grade (MR-TRG) and Correlation With Pathologic Endpoints Score in NRG Oncology GI002

Total neoadjuvant therapy (TNT) including chemotherapy (chemo) and concurrent chemo and radiotherapy (RT) is a promising strategy for rectal cancer. Characterizing tumor regression during TNT represents an important area of research. We report a prospective validation study of the Magnetic Resonance Tumor Regression Grade (MR-TRG) using MRIs from NRG-GI002, a phase II trial of TNT for rectal cancer.This was the a priori designed imaging biomarker study of NRG-GI002 seeking to correlate the MR-TRG with the pathologic Neoadjuvant Rectal score (NAR) and pathologic complete response (pCR). 110 patients (pts) were needed with 2 MRI's, 1 pre-TNT and 1 post. Three diagnostic radiologists independently reviewed each MRI and completed a consensus read. Radiologists' assessment of complete response (mriCR) was tested for its positive predictive value (PPV), negative predictive value (NPV), sensitivity (sen), and specificity (spec) with pCR. Chi-squared test was used for association of mriCR and pCR, and Wilcoxon-Mann-Whitney test was used for association of MR-TRG and pCR. Spearman Rho was used for association of MR-TRG/mriCR and NAR. P-values < .05 (2-sided) were considered significant. Each reader's T-stage, N-stage, extra-mural vascular invasion (EMVI), MR-TRG score and diffusion weighted imaging (DWI) assessment was evaluated for inter-reader variability by Kappa statistics. Kappa values of agreement were interpreted as: poor, < 0.0; slight, 0.0-0.2; fair, 0.2-0.4; moderate, 0.4-0.6; substantial, 0.6-0.8; and almost perfect, 0.8-1.0. All analyses were performed using a data management and decision management software. Radiologists were blinded to pathologic data.A total of 126 patients, from 76 institutions, had 2 MRI's (pre-TNT and post), 3 radiologists completed 756 MRI interpretations. Of 126 patients, 29% were female (N = 37), 85% white (N = 107) and median age was 55 (24-76). Individual and consensus MR-TRG scores were highly associated with pCR (P < 0.01) and NAR (Rho = .39, P < 0.001). The addition of DWI to MR-TRG improved both sen and spec over MR-TRG alone (P = 0.035). On the consensus read for mriCR, sen = 53.3%, spec = 70.7%, PPV = 42.1%, and NPV = 79.1% compared to pCR, and was highly associated (P = 0.02). The Kappa agreement score for T-stage, N-stage, and EMVI was 0.34, 0.67, and 0.39 reflecting fair, substantial, and fair agreement respectively. The Kappa agreements score across readers were 0.26 for MR-TRG and 0.32 for DWI, reflecting fair agreement. The mriCR, had a Kappa statistic of 0.85, reflecting near perfect agreement.MR-TRG is significantly correlated with pathologic NAR score. Binary assessment of CR, using MR-TRG and DWI, had near perfect agreement across readers. The addition of DWI to MR-TRG improved both the sen and spec, reflecting utility of DWI in this setting. Correlation of mriCR with pCR was statistically significant. Notably, PPVs here were limited, implicating the need for stronger biomarkers when planning a national rectal organ preservation study. NCT02921256.

Clinical Outcomes of Histologically Verified Salivary Ductal Carcinomas: Retrospective Analysis of 89 Patients Treated Over 47 Years

Salivary duct carcinomas (SDC) make up < 2% of salivary duct tumors but are very aggressive with a low 5-year survival rate of 35%. This series reports long term outcomes of patients with SDC treated at a single institution.Patients ≥18 years with histological confirmation of SDC treated with curative intent from 1961-2018 were included in this analysis. Patients were excluded if treatment was palliative intent (N = 14), and if staging (N = 4) or locoregional control (LRC) status (N = 7) was not recorded. 89 patients (74% male) met criteria for inclusion. Median age was 66 years (range: 32 - 89). AJCC 8 staging of patients were as follows: 13% (I), 6% (II), 12% (III), 62% (IVa), and 7% (IVb). 67% of patients were lymph node positive. Kaplan Meier analyses were used to estimate LRC and OS rates. Bivariate regression analyses using disease and treatment characteristics (i.e., perineural invasion (PNI), extracapsular extension (EE), vascular invasion (VI), CN VII sacrifice, extraparenchymal involvement (EI)) for prediction of LRC and OS were performed.Median follow-up was 48.5 months (0.4-343 mo). Most patients were treated with combined modality therapy; 82% (n = 73) undergoing curative surgery followed by adjuvant radiotherapy (RT) with (26%, n = 23) or without (56%, n = 50) concurrent chemo while 4.5% (n = 4) were treated with definitive RT; 2.3% (n = 2) receiving concurrent chemo. 13.5% (n = 12) were treated with surgery alone. Crude post-treatment LRC after surgery alone, surgery followed by adjuvant RT, and definitive RT alone were 66.7, 78.1 and 0% (P = 0.002), respectively. The odds of achieving LRC were diminished with incidence of VI (odds ratio (OR) = 0.07, P = 0.02), EI (OR = 0.3, P = 0.03), and T3/T4 staging (OR = 0.3, P = 0.03). Chemotherapy did not influence LRC. The occurrence of distant metastases was associated with PNI (OR = 5, P = 0.003) and EI (OR = 2.6, P = 0.03). EI status was also associated with a shorter time to recurrence (26 vs 17.3 mo, P = 0.04). Median overall survival (OS) was 55.3 months (41.7-81.7 95% CI) with 82% surviving at 2 years, 47% at 5 years, and 28% at 10 years. Failure to achieve LRC (81.7 vs 36 mo, P < 0.001), distant metastases (108.5 vs 41.7 mo, P < 0.001), VI (86.2 vs 46.8 mo, P = 0.046), T3/T4 staging (125.8 vs 48.8 mo, P = 0.02), PNI (88.1 vs 48.8 mo, P = 0.03), and EI (108.5 vs 47.3 mo, P = 0.004) were found to significantly reduce median OS.SDC is an aggressive tumor that requires a multimodality treatment approach. Patients analyzed here had a 5-year survival greater than what is typically reported for SDC (47 vs. 35%). Definitive radiotherapy was less likely to control gross disease and should be reserved for the adjuvant setting if surgery is an option. We identified incidence of extraparenchymal involvement, perineural and vascular invasion as negative prognostic indicators of disease control and survival.

Low-Dose Ultra-Fractionated Radiotherapy as a Chemosensitizer of Neoadjuvant Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma: A Preliminary Results of the Phase II Trial

The main failure model of locally advanced nasopharyngeal carcinoma (LANPC) is local failure and distant metastasis. N stage is a prognostic factor for NPC. Some characteristics of lymph nodes, such as the size, number, laterality, extra-nodal neoplastic spread and central necrosis, were the high-risk factors for treatment failure. Nowadays, neoadjuvant chemotherapy followed with concurrent chemo radiotherapy was recommended for LANPC patients. Low-dose radiotherapy (LDRT), which is < 100 cGy, induces enhanced cell killing in vitro and in vivo by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. Few studies reported about it. Recently, a single arm study showed it could improve the ORR to 82% for head and neck squamous carcinoma when combined with neoadjuvant chemotherapy. So, we aimed to investigate the efficacy of LDRT combined with neoadjuvant chemotherapy for high-risk LANPC.Squamous III-IVA NPC patients (UICC/AJCC 8th) with high-risk factors of lymph nodes were prospectively enrolled in the study. The high-risk factors should include one of these followings: lymph node with central necrosis, extranodal neoplastic spread, contrast-enhancing rim or the shortest diameter of lymph nodes ≥3cm. 3 cycles of neoadjuvant chemotherapy were given, the regimen was docetaxel (75mg/m2 D1) and cisplatin (75mg/m2 D1). LDRT was delivered as 50 cGy per fraction twice a day for gross nodal disease on D1 and D2 of neoadjuvant chemotherapy. All the patients received MRI scan before and after the neoadjuvant chemotherapy. Propensity score matching was used to select the patients as control group. RECIST criteria was used to evaluate the ORR.From Jun 2020 to Jan 2021, a total of 27 patients were enrolled in the study. Another 27 patients were matched for control group. For the whole patients, the median age were 43 years. III and IVA Clinical stage were 25.9%, 74.1% and 29.6%, 70.4% respectively for LDRT and control group (P = 0.761). As for the lymph nodes, the ORR of LDRT group was significantly higher than control group (100% vs 85.2%, P = 0.038). The average regression rate of lymph nodes was 89.4% in LDRT group, CR and PR was 7.4% and 92.6%. However, the average regression rate of it was only 56.24% in control group. There was no CR, PR and SD were 88.9% and 11.1%. For the primary tumor, there was no significant difference. But we found the ORR of it was higher in LDRT group (96.3% vs 81.5%, P = 0.083). And the average regression rate was 57.5% and 38.3% respectively in LDRT and control group.LDRT combined with neoadjuvant chemotherapy could improve the ORR for primary tumor and lymph nodes in high-risk LANPC patients, especially for lymph nodes. This new treatment model could be a promising strategy to improve local control, and needed to be confirmed in the future practice.

COMPARISON OF COMPLIANCE AND RESPONSE FOR NEOADJUVANT CHEMOTHERAPY FOLLOWED BY CONCURRENT CHEMO RADIATION VERSUS CHEMO RADIATION ALONE IN CARCINOMA CERVIX FIGO STAGE IVA- A SINGLE INSTITUTION EXPERIENCE.

Aims/Objectives: Cervical cancer is the second most cancer in women in India. Patients presenting with stage IVa have 5 year survival rates of only 16% and are not able to complete the full course of radiation due to advance disease. The aim of this retrospective study is to study the compliance of the stage IVa patients to neoadjuvant chemotherapy (NACT) followed by concurrent chemo radiotherapy and their completion of radical dose of radiation and subjective response in comparison to patients without NACT. Materials and Methods: We retrospectively studied stage IVa cervical cancer patient's case sheets from January 2019 to June 2020. The patients are divided in to 2 arms: Arm-A : 11 patients - who received NACT with Paclitaxel 175mg/m2 and carboplatin AUC 6 every 3 weeks of 4 cycles followed by external beam radiotherapy(EBRT) of 50 Gy/25 fractions with weekly cisplatin of 40 mg/m2, followed by brachytherapy of 700cGy of 3 fractions. Arm-B: 9 patients-who received external beam radiotherapy (EBRT) of 50 Gy/25 fractions with weekly cisplatin of 40 mg/m2, followed by brachytherapy of 700cGy of 3 fractions. The compliance to complete radical dose of radiotherapy with concurrent chemotherapy and response in patients with and without NACT were compared Results: Arm A: 10 patients (91%) completed radical dose of RT and weekly cisplatin, one patient (9%) defaulted for EBRT, all patients tolerated 4 cycles of NACT. During 3 months follow up 1 patient (9%) developed liver secondaries and 1 patient (9%) developed other complication (jejunal obstruction) 2 patients suffered dysuria(18%) and 7 (64%) patients asymptomatic. Arm B: 4 patients (44.5%) completed radical dose of RT and 5 patients (55.5%) defaulted radiation [one for EBRT and 4 for HDR] During 3 months follow up one patient (11%) developed liver secondaries and 1(11%) developed uraemia and died (both these patients completed radical dose), 2 (22.2%) patients with dysuria,2 (22.2%) patients with bleeding p/v and 3(33.3%) patients are asymptomatic. Patients who defaulted for radical dose of concurrent RT were more in arm -B (55%) when compared to arm- A(9%) More patients are asymptomatic in arm-A(64%) than arm-B(33%). Conclusions: Response and compliance to treatment was better in the patients who received NACT followed by concurrent chemo radiation and are able complete treatment and majority of them are asymptomatic. From this it may be concluded that NACT may be considered in stage IVa cervical cancer. However a prospective trial with large number of patients is needed to come to a conclusion.

English

BACKGROUND Concurrent chemotherapy is a well-established treatment modality for locally advanced head and neck cancer. The concept of concurrent chemotherapy and radiation was introduced in an attempt to improve the local control and possibly influence the survival because of the high rate of local and distant failures observed with the combination of surgery and postoperative radiation. The relevance of this study was to assess the efficacy of our treatment and patience compliance and also study the effect in patients treated with cisplatin based concurrent chemo radiotherapy in advanced head and neck cancer. METHODS The prospective study was conducted in the Department of Radiotherapy, Government Medical college, Thrissur, Kerala comprising the newly diagnosed patients with locally advanced head &amp; neck cancers over one year. Conventional radiotherapy with a dose of 66 Gy in 33 fractions over 6.5 weeks was given concurrently with Inj cisplatin 100 mg / 2 IV every 3 weeks and periodically followed up for one year. RESULTS This study revealed that complete response rate was higher in 61 – 70 year age group compared to lower age groups. Complete response cases were slightly higher in T1 disease compared to higher stages. Regarding nodal status, complete response and DFS were more in N0 tumours and worst in N3 tumours. It was found that complete response rates were slightly higher in stage III than stage IV. Comparing the grade of the tumour, complete response cases were slightly higher in WD and MD compared to PD. Complete response rate and disease free survival (DFS) were slightly higher in cases who had more than two chemotherapy cycles compared to one cycle. CONCLUSIONS Concurrent chemo radiation was not well tolerated in our study group. Only 23.5 % patients were able to complete the planned treatment. The positive side was that complete response was found in about 79.4 % of study patients &amp; DFS at one year was 80 %. KEY WORDS Concurrent Chemo Radiation, Head and Neck Cancer, Cisplatin

Radiotherapy versus Surgery in Early-Stage HPV-Positive Oropharyngeal Cancer.

PurposeThis study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus–positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment.Materials and MethodsThis multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I–II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT.ResultsWith a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding.ConclusionWe found no differences in OS, PFS, and LC between upfront RT and surgery in stage I–II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

Concurrent chemoradiation in the management of newly diagnosed glioblastoma multiforme: Retrospective review of single center experience over a period of 10 years.

e14028 Background: Glioblastoma Multiforme (GBM) is the most common primary intracranial tumour of the brain. The standard of care first line management is maximum safe debulking followed by concurrent chemo radiation (Stupp et al, 2005). In spite of further recent advances, median survival still remains poor and ranges between 14 to 21 months, especially in the MGMT unmethylated group. There are no randomised trials investigating less than 6 cycles of adjuvant temozolomide (TMZ). In our study we retrospectively analyse the impact on overall survival (OS) and progression free survival (PFS) in cases where adjuvant treatment has been discontinued due to toxicity or patient’s fitness Methods: We collected data from 2007 to 2016 for a cohort of patients who underwent adjuvant treatment for GBM following histological diagnosis. The final analyses included patient’s who completed concurrent chemoradiotherapy to a dose of 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ chemotherapy Results: Of 110 patient cohorts, 57% of patients completed adjuvant chemo radiotherapy followed by 4-6 cycles of adjuvant TMZ, 43% received 3 or less cycles of TMZ. Overall PFS was 11.9 months. Those that completed 4 or more cycles of adjuvant TMZ had an improved PFS (Log rank test P-value 0.001) versus those that completed 3 or less cycles. On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Median overall survival was 16 months for the whole group, but was 10 vs. 20 months for the two groups. On cox analysis we also identified second line chemotherapy had a significant impact on OS (cox model P-value 0.002) Conclusions: We identified patients receiving three or fewer cycles of adjuvant TMZ had poorer outcomes. Second-line chemotherapy improved outcomes at relapse regardless of redo surgery.

Demographical differentials of lung cancer survival in Bangladeshi patients.

10570 Background: Lung Cancer is the leading cause of cancer-related mortality and most common cancer in worldwide with more than a million deaths annually. 20.8% cancer related death caused by lung cancer and more than half of lung cancer occurred in Asia. Differences In the epidemiology of lung cancer among the developing country may shed light on possible genetic and demographical influences on lung cancer survival. Demographic stratification of lung cancer patients of Bangladesh is remain unclear due of lack of data We tried to figure out the demographic pattern and its impact on survival in Bangladeshi lung cancer patient. Methods: Previously diagnosed primary lung cancer patients attending Medical Oncology department of National Institute of cancer research and Hospital, a tertiary care center of Bangladesh, between 2018 and 2019 were included. Demographic and clinical data were collected retrospectively from the medical records. Results: A total of 1868 consecutive patient (1580 males, 288females) diagnosed to have lung cancer; Mean age was 60 years which quite early compare to other countries. Older than 70-year age groups had worse survival outcome (hazard ratio 1.04: 95% confidence interval: 1.17–1.68). Below 50-year group had better outcome with standard adjuvant or palliative chemotherapy whereas older groups had better survival with sequential radiotherapy and chemotherapy or concurrent chemo radiation (Hazard Ratio 0.45; 95% confidence interval: 0.30–0.67). Sex was not a predicting factor for overall survival (Hazard ratios 1.04 95% confidence interval 0.89- 1.22, P = 0.621). But, Male had better treatment response than the female (Hazard ratio and 95% confidence interval: 0.51 and 0.42-0.61, P = &lt; 0.001). Education level had significant impact on survival outcome (Hazard ratio 0.58 and 95% confidence interval: 0.47-0.71, P = &lt; 0.001). Underweight group had worse survival than the normal BMI group (Hazard ratio1.18 and 95% confidence interval 1.05-1.31, P = 0.005). Having the Comorbid condition at the time of diagnosis had shorter survival (Hazard ratio 1.16 and 95% confidence interval 1.04-1.30 P = 0.007). Histological variation had no survival benefit among the squamous, small cell or other histological types (p = 0.214, 0.494, 0.658 respectively). But adenocarcinoma or small cell carcinoma had better treatment response outcome. Eastern Cooperative Oncology Group performance status (ECOG-PS) 4 had worse outcome (Hazard ratio 1.95, 95% confidence interval 1.37–2.79; P = &lt; 0.001). Conclusions: The socio-demographic related survival in lung cancer needs to be fully elucidated because of its implication in the design of experimental protocols for targeted chemoprevention, early disease screening, molecular marker based staging, and individualized treatment. Due to its extraordinary disease burden and the international variability in demographic variables, the lung cancer requires continual monitoring.

CONCURRENT CHEMO-RADIOTHERAPY OF WEEKLY PACLITAXEL VERSUS WEEKLY CARBOPLATIN IN LOCALLY ADVANCED HEAD AND NECK CARCINOMAS UNFIT FOR CISPLATIN

Background: Chemoradiotherapy have an important role in the treatment of locally advanced head and neck cancers, in old age patients with, renal and cardiac dysfunction ineligible for cisplatin, We compared weekly Taxol versus weekly carboplatin .AIM: Our study aiming to comparing the efficacy and toxicities of chemo radiotherapy of weekly Taxol versus weekly carboplatin in locally advanced head and neck carcinoma. PATIENT AND METHODS: The study divided in two arms, paclitaxel arm; 25patients treated by weekly paclitaxel 40mg/m2 with radiotherapy and carboplatin arm; 25 patients treated by weekly 150mg carboplatin with radiotherapy. The three-dimensional radiotherapy planned (3DCRT) was 65 to 70 GY and 1.8 -2 GY /fraction, 5 fractions/week in 6-7 weeks. RESULTS: There was an insignificant 5-year disease free survival was 79.5% in carboplatin arm versus 84.6% in paclitaxel arm and 5-year OS was an insignificant 76% in carboplatin arm versus 72% in paclitaxel arm (p-value=0.646) . A 44% of both arms had overall complete remission. A 16% of patients received carboplatin had grade III/IV mucositis. Patients in paclitaxel arm had more grade II neuropathy (60%). A comparable rate of neutropenia had occurred in both arms. CONCLUSION: Both arms of concurrent chemo radiotherapy had acceptable toxicities with good quality of life response to treatment where 44% of both arms had complete response (p-value=0.623). There was an insignificant 5-year disease free survival was 79.5% in carboplatin arm versus 84.6% in paclitaxel arm and 5-year OS was an insignificant 76% in carboplatin arm versus 72% in paclitaxel arm (p-value=0.646).

Small cell neuroendocrine carcinoma of subglottis: a case report

&lt;p class="abstract"&gt;Small cell carcinoma is an uncommon type of malignant epithelial neuroendocrine neoplasm. It is most commonly of pulmonary origin and only less than five percent of all tumours are extrapulmonary. Esophagus, stomach, colon and rectum, gall bladder, head and neck, urinary bladder, prostate, skin and cervix are the most common extrapulmonary sites. Small cell carcinoma of larynx accounts for less than one percent of all laryngeal neoplasms. It is a highly aggressive neoplasm with poor prognosis. It most commonly affects supraglottis in males who are heavy smokers in their sixth and seventh decades. Various paraneoplastic syndromes can also be associated with the neoplasm. More than 90% of small cell laryngeal neoplasms present with metastatic disease. Surgery is not considered the initial treatment of choice; concurrent chemo radiotherapy is proven to provide longer survival. We report the rare case of extrapulmonary small cell neuroendocrine tumour in subglottis in a non-smoker female patient.&lt;/p&gt;

Abstract PO-054: Correlation of hematological toxicity with the bone marrow radiation dose and volume during concurrent chemo radiation in patients with cervical cancer

Abstract Aims &amp; Objective: Hematological toxicity is common in patients with cervical cancer treated with concurrent chemo radiotherapy (CT-RT), so the purpose is to assess this hematological toxicity and correlate the toxicity with the dose and volume of bone marrow included in the field of radiation. Materials &amp; Methods: Twenty-five patients with histologically proven cervical cancer attending to our cancer center from July 2008-August 2009 were the subjects of this study. Patients were treated on 6 MV linear accelerator with a radical intent with concurrent chemotherapy using cisplatin 50 mg weekly. The planning CT was done for all the patients before the treatment and contouring of the pelvic bone marrow apart from other organs at risk was done. Hematological toxicity was assessed using RTOG common toxicity criteria weekly during and at 2 weeks after the completion of the treatment. Results: A total of 25 patients on CT-RT treatment were assessed. Sixteen patients were in locally advanced stage. The variation in HB, TLC, Platelets, and ANC counts from the baseline to 2 weeks after chemo radiotherapy were assessed. Grade II anemia was observed in 12 and Grade III in 2 patients. There were no toxicity as far as WBC and platelets were considered. There was also no correlation between the volume of bone marrow included in the field of irradiation and appearance of anemia. Conclusion: CT-RT for cervical cancer is safe and is associated with minimal hematological toxicity in the form of anemia. The toxicity is same for different volumes of bone marrow included in the field of irradiation with both conventional as well as 3DCRT technique. The toxicity observed is probably contributed by Cisplatin. Citation Format: Irappa Madabhavi, Ragavendra Sagar, Apurva Patel, Malay Sarkar. Correlation of hematological toxicity with the bone marrow radiation dose and volume during concurrent chemo radiation in patients with cervical cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-054.

Pragmatic recruitment of memantine as the capping group for the design of HDAC inhibitors: A preliminary attempt to unravel the enigma of glioblastoma.

Hurdled and marred by the notorious nature of glioblastomas (GBM) in terms of resistance to therapy and limited drug delivery into the brain, the anti-GBM drug pipeline is required to be loaded with mechanistically diverse agents. The consideration of HDAC inhibition as a prudent approach to circumvent the resistance issue in GBM spurred us to pragmatically design and synthesizes hydroxamic acids endowed with CNS penetrating ability. By virtue of the blood brain barrier permeability (BBB), memantine was envisioned as an appropriate CAP component for the construction of the HDAC inhibitors. Diverse linkers were stapled for the tetheration of the zinc binding motif with the CAP group to pinpoint an appropriate combination (CAP and linker) that could confer inhibitory preference to HDAC6 isoform (overexpressed in GBM). Resultantly, hydroxamic acid 16 was identified as a promising compound that elicited striking antiproliferative effects against Human U87MG GBM cells as well as TMZ-resistant GBM cells and P1S cells, a concurrent chemo radiotherapy (CCRT)-resistant/patient-derived glioma cell line mediated through preferential HDAC6 inhibition (IC50=5.42nM). Furthermore, 16 exerted cell cycle arrest at G2 phase, induced apoptosis in GBM cells at high concentration and exhibited high BBB permeability. To add on, in-vivo study revealed that the administration of compound 16 prolonged the survival of TMZ-resistant U87MG inoculated orthotopic mice. Overall, the cumulative results indicate that 16 is a tractable CNS penetrant preferential HDAC6 inhibitor that might emerge as a potent weapon against GBM.

Prevalence of sensorineural hearing loss in patients with head and neck malignancy who underwent chemotherapy and or radiotherapy

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Our study aimed to focus on the importance of the rate at which the sensory neural hearing loss (SNHL) is caused by chemotherapy (CT) and or radiotherapy (RT). This study also tells about the importance of informing the patient and the caretakers prior to the start of treatment for carcinoma, so that they can be prepared for it if it happens. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Total 75 patients who were diagnosed to have any form of head and neck malignancy formed the study group. Pure tone audiometry was recorded pre-treatment, one month after treatment and six months after treatment. All the data obtained were bio statistically analysed by running in SPSS software version 26. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; There is a correlation between CT, RT and concurrent chemo radiotherapy (CRT) and SNHL. It is also found that most of the patients who have undergone CRT suffered SNHL in the long run. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; It is high time the patients are made aware of the side effects like SNHL before the start of the proposed treatment. This will allow them to be prepared and then face it. &lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Paclitaxel Based CCRT Is an Acceptable Alternative for Cisplatin Based CCRT in the Treatment of Locally Advanced (Stage IVA) Head Neck Carcinoma

<i>Introduction:</i> Head neck carcinoma is the sixth most common cancer in the world. Concurrent chemo radiation became standard protocol for patients with locally advanced squamous cell carcinoma of head neck where curable surgery is not feasible. <i>Study Design and Objective:</i> This quasiexperimental study done to compare the treatment response and acute toxicities with the treatment of low dose weekly Paclitaxel with radiation versus weekly Cisplatin with radiation therapy for histologically proven Stage- IVA squamous cell carcinoma of head neck. <i>Methods:</i> All the patients were divided in two groups. Arm-A, 45 number patients received injection Paclitaxel 40 mg/m², i/v in 1 hr. infusion weekly for 6 weeks and in Arm- B, 45 number patients received injection Cisplatin 30 mg/m², i/v in 2 hrs infusion weekly for 6 weeks. All patients received 66 Gray (Gy) radiation at the rate of 2 Gy/day, 5 fractions in a week for 6.5 weeks. <i>Results:</i> In this study about 65.55% patients were smoker. Most common sub site was larynx (41.46%) followed by oral cavity (25.00%) The most common presenting features were cervical lymphadenopathy (100.00%) followed by pain (70.00%), sore throat (43.33%) and hoarseness of voice (41.11%). Complete response showed in the patients of Arm-A, 73.33% among the smoker and 66.67% in non-smoker, whereas 72.41% in smoker and 62.50% in non-smoker showed complete response in the patients of Arm-B. Common toxicities related to treatment were mucosities, skin reaction, vomiting, nausea, weight loss, anaemia, leucopcnia, thrombocytopenia and diarrhoea. The toxicities in Arm-A were more than that of Arm-B, but were manageable. <i>Conclusion:</i> In this study it is evident, the concurrent chemo radiotherapy with weekly Paclitaxel is suitable alternative when Cisplatin cannot be given safely.