Locoregional Response Research Articles

Short term clinical outcomes of accelerated hypofractionated radiotherapy in inoperable non-small cell lung cancer patients.

This study aimed to evaluate short term clinical outcomes of accelerated hypofractionated radiotherapy (AHR T) regarding locoregional response (LRR), symptoms relief and acute toxicities in non-small cell lung cancer (NSCLC) patients. The radical treatment for inoperable NSCLC is intolerable for some patients. An alternative RT regime should be considered for them. Inoperable NSCLC patients who could not tolerate radical treatment were treated with AHRT (45 Gy in 15 fractions over three weeks) by using the 3-dimensional conformal (RT) technique. The LRR was assessed by chest computed tomography (CT) performed before and 6 weeks after RT. Relief of symptoms such as cough, dyspnoea and chest pain was evaluated during RT and 6 and 12 weeks after RT, compared with the status before RT. Treatment-related acute toxicities such as dysphagia and radiation dermatitis were observed during and 6 and 12 weeks after RT. Total 65 patients (seven patients of stage II and fifty-eight patients of stage III) were included. Partial response was seen in 70.8% of patients, and stable disease was seen in 29.2% while there was neither complete response nor progressive disease after RT. Statistically significant associations were found between tumour response vs. pre-treatment tumour size and tumour response vs. performance status of the patients. Satisfactory symptom relief was found after RT, but severe acute dysphagia and radiation dermatitis (more than grade 3) were not observed. Satisfactory LRR, symptom relief and acute toxicities were achieved by this regime. Long term studies are recommended to evaluate late toxicities and survival outcome further. TCTR20200110001.

874P Concurrent chemoradiation with cisplatin alone versus cisplatin and capecitabine in treatment of locally advanced head and neck cancer

Concurrent chemoradiotherapy is the standard treatment of locally advanced head and neck cancers. The objective of this study was to assess the locoregional response rates and acute toxicity in patients with locally advanced head and neck carcinoma treated with concurrent chemoradiation with cisplatin versus cisplatin and capecitabine.

Interim analysis of a phase II study of simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) in combination with 5-FU and mitomycin-C among patients with locally advanced anal canal cancer.

e15501 Background: Concomitant radiochemotherapy is the standard treatment of locally advanced epidermoid anal canal carcinoma (EACC) but conventional radiotherapy (RT) frequently induces significant non-hematological toxicities, resulting in long treatment breaks. Given the numerous anatomic pelvic structures, EACC has become of interest for Intensity-Modulated Radiation Therapy (IMRT) despite the induced cutaneous toxicities responsible for RT breaks. Given the deleterious effect of treatment duration on local control and survival in other epidermoid cancers, continuous IMRT is challenging to control EACC. Several SIB-IMRT schedules provided similar results with moderate doses and schedules delivering higher doses with short breaks. Yet, standard SIB-IMRT schedule in EACC still not exists. We propose to concomitantly assess the safety and efficacy of continuous SIB-IMRT without planned breaks and concurrent chemotherapy (CT) to improve the treatment of locally advanced EACC by reducing the proportion of patients (pts) requiring RT breaks for toxicities. Methods: The CANAL-IMRT-01 phase 2 trial (NCT02701088) targets pts with histologically proven EACC candidate for concomitant RT of pelvic and inguinal nodes plus CT. Applying a two-step Bryant & Day design, the main criterion is based on both efficacy and safety. Efficacy is defined as the proportion of pts alive with no local disease progression 3 months after the end of IMRT; safety is defined as the proportion of pts with no RT breaks required by grade ≥3 toxicities. Assuming the unacceptable and acceptable proportions of pts without toxicity requiring IMRT break are 60 and 80% respectively, the unacceptable and acceptable 3-month-progression-free-survival are 80 and 90%, 14 assessable pts at first step and 46 in the second are required (alpha risk 5%, 90% power). To anticipate a 10% drop out rate, 16 pts were needed in first step, with ≥11 objective local responses and ≤6 toxicity-induced IMRT breaks to pursue. Treatment consists in 50 days of concomitant CT (2 cycles of 5FU and Mitomycin-C) and SIB-IMRT delivered by helical tomotherapy: 61.2Gy/1.7Gy to the primary tumor, 57.6Gy/1.6Gy to involved nodes, and 54/1.5Gy to elective pelvic lymph nodes. Results: From December 2015 to June 2017, 16 pts were enrolled: 11 female (73%), median age 62 [55-66]. 15 pts were assessable for efficacy and safety. All 15 pts had a 3-month locoregional response (12 complete responses, 3 partial responses). SIB-IMRT breaks were required by toxicities for 4 out of 15 pts: G1 radiodermitis, G2 inguinal and epithelitis, G1 fever, G3 anorexia and vertigo. Conclusions: The planned interim analysis of continuous SIB-IMRT plus CT allowed pursuing this phase 2 trial to assess the relevance of such schedule for locally advanced ASCC. Enrolment is still ongoing. Clinical trial information: NCT02701088.

205P A study on organ preservation in muscle invasive urinary bladder cancer patients with intensity modulated radiotherapy and concurrent single agent cisplatin in south Indian population

The standard care for muscle invasive bladder carcinoma (MIBC) in the United States for a long time was radical cystectomy where as in Europe, it is radical radiotherapy or multidrug regimen neoadjuvant chemotherapy followed by radiotherapy. In spite of the importance in terms of incidence, prognosis and cost, bladder cancer research remains significantly underfunded so the studies and data on organ preservation in MIBC in India are less explored. We analyzed the data of 30 patients of MIBC from 2016-2018 who underwent primary transurethral resection of bladder tumour (TURBT) followed by IMRT with 64.8 Gy and weekly cisplatin at dose of 40 mg/ m2 with median follow up of 10 months. The role of various factors like tumour stage, histopathology, grade, complete TURBT, obstructive uropathy on locoregional response and disease free survival was evaluated. Local reactions evaluated using CTCAE criteria version 5.0. Statistical analysis was done using SPSS version 23.0. Table: 205PDemographic and disease characteristicsAgeMedian – 68 Yrs Range – 52 - 80 YrsSexMale – 86.7% (n=26) Female – 13.3% (n=4)TurbtComplete – 33.3% (n=10) Incomplete – 66.7% (n=20)HistopathologyTransitional – 86.6%(n=26) Squamous – 6.7% (n=2) Adeno CA – 6.7% (n=2)GradeGrade I – 6.7% (n=2) Grade II – 26.6% (n=8) Grade III - 66.7% (n=20)Tumour StageT2 – 53.3 % (n=16) T3 – 33.3 % (n=10) T4 – 13.4 % (n=4)Obstructive UropathyPresent – 33.3 % (n=10) Absent – 66.7% (n=20)Locoregional ResponseComplete – 73.3% (n=22) Partial – 20% (n=6) Progression – 6.7% (n=2) Open table in a new tab After the treatment, the complete locoregional response (LRR) was 73.3%. Early (T2 stage) tumours (p= 0.043) and patients without obstructive uropathy (p= 0.039) have shown significant LRR. Patients with complete TURBT, Low grade tumours shown increased response though statistically not significant. The overall disease free survival in this study for the preserved bladder patients is 53.3%. Patients without obstructive uropathy have shown significant DFS of 70% (p=0.026). Improved DFS of patients with T2 stage tumours (75%), complete TURBT (60%), low grade tumours was observed though statistically not significant. GU toxicities like dysuria, burning micturition in 40% of patients, increased frequency of micturition in 20% of patients, gastro intestinal toxicities like constipation (40%), pain abdomen (6.7%) were observed during followup and all these are grade I,II and managed well with supportive treatment. Bladder preservation in more than 70% of patients in this study supports the general concept of organ sparing treatment in oncology. The high response rate and DFS were observed in south Indians with complete TURBT, early stage tumours, no obstructive uropathy and low grade tumours. The genito urinary & gastro intestinal toxicities are comparatively less, probably in view of using IMRT technique and single agent cisplatin.

Concurrent Chemoradiotherapy in Locally Advanced Squamous Cell Carcinoma of Head and Neck with Capecitabine and Weekly Cisplatin

AIMS & OBJECTIVES: To assess the immediate loco regional response rates and acute toxicity in patients with locally advanced squamous cell carcinomas of the head and neck in Conventional radiotherapy with weekly Cisplatin and Capecitabine. MATERIALS AND METHODOLOGY: Single arm prospective study with 30 consecutive patients with locally advanced head and neck cancer presented to the department of radiotherapy, Madras medical college, Chennai. All patients were treated with conventional radiotherapy 66Gy along with weekly Inj.Cisplatin 40mg/m2 and T.capecitabine 500mg/m2 twice daily along with radiation. The immediate loco regional response rates were assessed clinically and radiologically 6 weeks after concurrent chemo radiotherapy. The toxicity profile of the treatment was assessed with RTOG acute morbidity scoring criteria and CTCAE Version 4. RESULTS: Among 30 patients, Ca Oropharynx was 9 patients, followed by Ca Hypopharynx 8 patients, Ca Oral cavity with 7 patients and Ca Supraglottis 6 patients. 73% of patients had complete response and 27% had partial response. Toxicities observed in the study were Mucositis grade 3 in 5 patients and grade 4 in 2 patients; Skin reactions grade 2 in 2 patients. Leucopenia grade 2 in 2 patients. Systemic toxicity diarrhea grade 1 was only in 2 patients. There was no renal toxicity, hand foot syndrome in this study. There was no treatment related deaths in this study. CONCLUSION: Concurrent chemoradiotherapy with Inj.Cisplatin and T.Capecitabine in locally advanced squamous cell carcinoma of head and neck cancer is better regimen with manageable toxicity with higher complete response rate.

Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Therapy for Oesophageal Cancer Patients

Abstract Background Due to loco-regionally advanced at diagnosis, multi-modality treatment become optional for most of oesophageal cancer patients. With advanced imaging modalities and treatment machines, conformal radiotherapy with concurrent chemotherapy is the standard approach for non-surgical candidates. The aim of the present study was to assess immediate loco-regional response of neoadjuvant chemotherapy followed by concurrent chemoradiation therapy for oesophageal cancer patients. Methods This study include histologically proven oesophageal cancer patients who are refuse or unfit for surgery or unresectable disease with performance status 0-2. Neoadjuvant chemotherapy 2 cycles with cisplatin and 5FU regime followed by concurrent chemoradiation therapy (3D CRT, 50 Gy over 5 weeks with single agent cisplatin 75 mg/m2 on day 1 and 21 of radiotherapy was given. Response assessment was done with CT scan and endoscopy at 6th week after RT. Written informed consent was obtained from all patients. Results 26 patients were included in the study between August 2015 and December 2016. Commonest age group was within 5th to 7th decade of life. 16 were male (61.5%). 25 had SCCs (96.2%). 18 patient were with oesophageal cancer at middle third (69.3%). 15 present with grade III dysphagia (57.7%). 18 patients were stage III at the time of diagnosis. Total treatment compliance was 69.2%. During treatment, dysphagia grade revealed stable during first three weeks and worsened slightly over the last 2 weeks. During follow up period, 16 patients (61.5%) became free from dysphagia at 4th week and 19 patients (73.1%) at 6th weeks. On response assessment by CT and OGDS at 6th week, complete response was 15 (57.7%) and 18(69.3%) respectively and so overall response rate was 57.7%. Conclusion This results support the feasibility of neoadjuvant chemotherapy followed by concurrent 3D CRT for oesophageal cancer patients with potential for a cure effect with acceptable toxicities.

Second-look PET-CT following an initial incomplete PET-CT response to (chemo)radiotherapy for head and neck squamous cell carcinoma.

The limited positive predictive value of an incomplete response on PET-CT following (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) means that the optimal management strategy remains uncertain. The aim of the study is to assess the utility of a 'second-look' interval PET-CT. Patients with HNSCC who were treated with (chemo)radiotherapy between 2008 and 2017 and underwent (i) baseline and (ii) response assessment PET-CT and (iii) second-look PET-CT following incomplete (positive or equivocal scan) response were included. Endpoints were conversion rate to complete response (CR) and test characteristics of the second-look PET-CT. Five hundred sixty-two patients with HNSCC underwent response assessment PET-CT at a median of 17weeks post-radiotherapy. Following an incomplete response on PET-CT, 40 patients underwent a second-look PET-CT at a median of 13weeks (range 6-25) from the first response PET-CT. Thirty-four out of 40 (85%) patients had oropharyngeal carcinoma. Twenty-four out of 40 (60%) second-look PET-CT scans converted to a complete locoregional response. The primary tumour conversion rate was 15/27 (56%) and the lymph node conversion rate was 14/19 (74%). The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the second-look PET-CT were 75%, 75%, 25% and 96% for the primary tumour and 100%, 92%, 40% and 100% for lymph nodes. There were no cases of progression following conversion to CR in the primary site or lymph nodes. The majority of patients who undergo a second-look PET-CT convert to a CR. The NPV of a second-look PET-CT is high, suggesting the potential to avoid surgical intervention. • PET-CT is a useful tool for response assessment following (chemo)radiotherapy for head and neck squamous cell carcinoma. • An incomplete response on PET-CT has a limited positive predictive value and optimal management is uncertain. • These data show that with a 'second-look' interval PET-CT, the majority of patients convert to a complete metabolic response. When there is doubt about clinical and radiological response, a 'second-look' PET-CT can be used to spare patients unnecessary surgical intervention.

Abstract 452: Salivary HPV cell free DNA levels predict locoregional disease burden and response in oropharyngeal cancer

Abstract Purpose: The human papillomavirus (HPV) is linked to the majority of oropharyngeal squamous cell carcinomas (OPSCC). We have previously shown that tumor-derived HPV cell-free (cf)DNA can be detected and quantified in circulation with high sensitivity and specificity using droplet digital (dd)PCR1. Further, we have shown that plasma cfDNA levels correlate with disease burden and indicate treatment response in advanced OPSCC. In this study we pair plasma with salivary HPV cfDNA to understand its clinical application in monitoring locoregional spread of disease. Methods: We present a proof-of-concept prospective observational cohort of recurrent, metastatic (R/M) HPV+ OPSCC patients treated with standard systemic therapies or on active surveillance. We utilized ultrasensitive ddPCR to identify and quantify both plasma and salivary HPV cfDNA (subtypes 16, 18, 31, 33 and 45) at multiple time points. Salivary HPV cfDNA was normalized to total DNA concentration as measured by fluorometric quantification. We then compared matched plasma and normalized salivary HPV cfDNA concentrations at various timepoints with clinical parameters, such as tumor burden and therapeutic response. Results: Clinicopathologic data from 15 R/M patients revealed a male cohort with a median age of 57 at diagnosis. Five (33%) were on immunotherapy and 6 (40%) on standard chemotherapy during the study period (3 months). Salivary HPV cfDNA was detected in 13/15 (87%) samples (range 0-729 copies/mL) in at least one timepoint during the study (plasma cfDNA was detected in 12/15 or 80% of the cohort, range 0-12,949 copies/mL). All patients with measurable locoregional (LR) disease had detectable salivary cfDNA. While matched plasma and salivary cfDNA levels showed no correlation among individual patients, plasma cfDNA levels correlated with site of disease (LR, pulmonary or extra-pulmonary) (p < 0.001), while median salivary cfDNA levels strongly correlated with LR tumor burden (R = 0.81, p < 0.001). Salivary cfDNA levels declined by 80% of their baseline value within a median of 6.5 days among all patients with LR disease experiencing a response to treatment. Page 1 of 1 Conclusion: Our results suggest that high sensitivity salivary HPV cfDNA levels correlate with locoregional disease burden and can be an early indicator of locoregional treatment response, while our prior work has supported the role of plasma HPV cfDNA levels in monitoring metastatic disease. Evaluating paired plasma and salivary HPV cfDNA levels in a curative HPV OPSCC population is underway to further validate their prognostic and predictive potential. 1Hanna GJ, Supplee JG, Kuang Y, Mahmood U, Lau CJ, Haddad RI, et al. Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer. Ann Oncol. 2018;29:1980–6. Page 2 of 1 Citation Format: Glenn J. Hanna, Christie J. Lau, Umair Mahmood, Robert I. Haddad, Cloud P. Paweletz, Pasi A. Janne. Salivary HPV cell free DNA levels predict locoregional disease burden and response in oropharyngeal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 452.

Hypofractionated intensity-modulated radiation therapy with concurrent cisplatin in locally advanced oropharyngeal cancer: feasibility experience from a Government cancer centre of Eastern India in a resource-constrained setting

AbstractPurpose:Radiation therapy (RT), in combination with chemotherapy, is the mainstay in the treatment for locally advanced oropharyngeal cancer. We analysed the tumour response and the toxicity profiles in patients having locally advanced oropharyngeal cancers receiving hypofractionated intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with Cisplatin investigating the feasibility and radiobiological efficacy of the regimen, along with its use as a resource-sparing alternative for a high-volume centre.Material and Methods:The records of 41 eligible patients with locally advanced squamous cell carcinoma of oropharynx, registered from September 2015 to April 2017, treated with hypofractionated IMRT with concurrent Cisplatin, were analysed from the hospital database. Patients received concurrent chemo-radiation with 2 cycles of 3-weekly cisplatin on day 1 and day 22 along with hypofractionated IMRT, 55 Gy delivered in 20 fractions over 4 weeks. Patients were observed for any radiation reaction or chemotherapy toxicity at least once a week during the course of radiation therapy.Results:Twenty-nine patients (70·7%) achieved complete response and remaining 12 showed partial response. Acute grade 3 toxicity was observed mostly in the form of oral mucositis and radiation dermatitis. Both grade 3 oral mucositis and radiation dermatitis were seen in 15 patients (36·6%) and 7 patients (17%), respectively. The most common late toxicities were dysphagia and dry mouth. Twenty-five patients (61%) completed the overall treatment within 4 weeks’ duration.Conclusion:This hypofractionated regimen is feasible and was associated with tolerable acute and late morbidity and satisfactory locoregional response. Larger prospective, multi- institutional studies examining similar schedules may be undertaken to establish this as a standard practice, particularly for a high-volume centre.

Altered Fractionation Intensity Modulated Radiotherapy with concurrent chemotherapy in head and neck cancer : a feseability study

Purpose: To assess the loco regional response and toxicity of patients to concurrent chemo-radiation with 6 fractions/week using Intensity Modulated Radiotherapy in locally advanced head and neck cancers. (oropharynx and hypopharynx). Materials and Methods: 20 patients with Stage III and stage IV , squamous cell carcinoma of Head and neck were enrolled. Target Volume Delinetion was done in accordence with Danish Head and Neck cancer group (DAHANCA) contouring guidelines. Differential radiation dose of 70 Gy, 63Gy and 56Gy in 35 fractions using IMRT, delivered to GTV, CTV1 and CTV2 with weekly cisplatin with weekly assessment of response and toxicity. Results: The median age of the patients was 54 years ranging from 40 to 65 years. 14 and 6 patients had Hypopharyngeal and Oropharyngeal malignancy of squamous cell origin. 95 % of patients received 70 Gy in 35 fractions with 4 cycles of concurrent Cisplatin. 18 patients completed treatemnt within 45 days of OTT. 16 patients had complete response and 4 had partial response. Grade I, II dermatitis was observed in 70% and 30% of patients, respectively. 5 patienst developed Grade 2 and 1 patinet developed grade 3 leucopenia. 2 patients had weight loss of more than 10%. 85% oforopharyngeal cancers and 67% of hypopharyngeal cancers showed complete response. Nodal response was 100% complete in N1 & N2a, 92% and 0% in N2b and N3 lesions respicyively. TNM stage group wise the complete response rates were 100% in stage III, 92% & 0 % IVA & IVB. Conclusion: Accelerated fractionation with IMRT and concurrent chemotherapy is a feasible in locoregionally adanced head and neck cancers with acceptable toxicities and good locoregional response rates.

Current weaknesses of breast conserving strategies after neoadjuvant chemotherapy in breast cancer treatment

Locally advanced breast cancer (LABC) represents a worldwide major challenge, with a reported incidence reaching up to 90%. In such setting, current guidelines advise for neoadjuvant chemotherapy (NACT) as primary approach to provide effective systemic treatment while surgically down-staging the cancer at presentation. Despite advantages of NACT, ranging a reported locoregional response rate from 30% to 70%, several national surveys still describe higher mastectomy rates than expected. This phenomenon can be ascribed to radiology related factors, as the role of magnetic resonance imaging (MRI), despite having the highest correlation coefficient to final pathology, may still underestimate and overestimate tumor size, leading to surgical over and under treatment; surgeon related factors, as many breast surgeons routinely perform surgery based on pre-treatment characteristics rather than more appropriate posttreatment imaging and clinical results; patient related factors, as there is a well-documented tendency to prefer mastectomy instead of breast conservation therapy (BCT), in an attempt to reach better oncologic outcomes and hospital related factors, as there is too much variability between breast cancer centers, offering modern and minimally-invasive treatments and general hospitals, reporting a difficult access to advanced breast conserving strategies. In this context, the major part of this disinformation sequence in played by an important lacking of strong evidences, mostly regarding the oncologic outcomes of breast conserving surgery (BCS) and oncoplastic surgery (OS). Some recent high impact papers are reporting benefits of OS in LABC treatment, extending beyond improving cosmetic results, to the possibility of obtaining wider excisions with similar oncologic results as observed in patients submitted to classic BCS and mastectomy. Furthermore, what emerges from LABC literature is an imperative need of multidisciplinary breast centers worldwide diffusion, where breast-dedicated oncologists, radiologists and oncoplastic surgeons can offer patient-centered updated diagnostics, treatment protocols and surgical solutions, especially in a very delicate scenario, such as LABC treatment.

The Outcome of Neoadjuvant Chemo Radiotherapy and Surgery in Carcinoma Rectum: Our Experience

Introduction: Carcinoma of the rectum is not only a medical but a social problem. Adenocarcinoma of the rectum accounts for 30% of these cancers. Locally advanced cancers of the rectum i.e., stage 2 and 3 diseases prove to be a challenge with respect to its management. Present guidelines state that the use of neoadjuvant chemoradiotherapy to downstage the locally advanced carcinomas of the rectum to have a positive impact on not only the survival but also the quality of life post-treatment viz., by allowing better resection margins to preserve the sphincter mechanism by performing a coloanal anastomosis. Objectives: To assess the locoregional response rates determined by the measurement of margin of clearance from the anal verge, organ preservation (sphincter-saving operations), and histopathological findings in post CRT surgical specimen. Materials and methods: This study included a total of 33 patients which were diagnosed with locally advanced rectal cancer who presented in the department of General Surgery, Vydehi Hospital, Bangalore. The patients in this series were subjected to pre-operative CRT, loco-regional response rates and the number of sphincter preserving surgeries performed were assessed. Results: Downstaging of the tumor was achieved in 91% of the cases. Conclusion: From this study, an interpretation can be made that following CRT there is a significant downstaging and increased ability to perform sphincter-saving procedures.

A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors.

Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions.

Correlating Outcomes With Changes in Tumor Volume and 18F-FDG PET Characteristics During Radiation Therapy for Head and Neck Squamous Cell Carcinoma (HNSCC)

Correlating Outcomes With Changes in Tumor Volume and 18F-FDG PET Characteristics During Radiation Therapy for Head and Neck Squamous Cell Carcinoma (HNSCC)

Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma.

Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco- regional control with a conventional schedule. Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin 40 mg/m2. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7 Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7 Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin 20 mg/m2/day was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were 65±12 and 48±4 days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade≥3 toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. In the setting of concurrent chemo- radiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.

Feasibility and response of concurrent weekly docetaxel with radical radiotherapy in locally advanced head and neck squamous cell carcinoma.

(1) To study the feasibility, adverse effects and response of concurrent weekly Docetaxel with radical radiotherapy in inoperable locally advanced head and neck squamous cell carcinoma. (2) To assess the compliance and tolerance of weekly Docetaxel with radiotherapy. Twenty one patients with stage III and IV head and neck squamous cell carcinoma satisfying inclusion criteria were selected and treated with conventional external radiotherapy of 70Gy in 35 fractions with weekly concurrent Docetaxel (15mg/sqm), administered one hour before radiotherapy. Assessment of toxicities and evaluationof response was carried out. Majority of patients had stage IV diseaseand 17/21 (81%) received the planned radiotherapydose of 70Gy and ≥4 cycles of weekly chemotherapy. Duration of treatment ranged from 7.1to 11.2 weeks. The toxicities noted were Grade III mucositis in 57% and grade III skin reaction in 23%, grade III dysphagia in 38% and grade II weight loss in 23% of patients. Systemic toxicities associated with chemotherapy were minimal and there was no dose limiting toxicities. The overall locoregional response at first follow up was 85%, with complete response of 70% and partial response of 15%. Concurrent Docetaxel is a feasible and suitable alternate to Cisplatin and 5-Fluorouracil chemotherapy with good patient compliance. The late toxicities and survival need to be followed up.

Immunomodulated anterior chemotherapy followed by concurrent chemoradiotherapy in locally advanced tongue cancer: An Institutional experience.

Context:Sequential induction chemotherapy with cisplatin and 5-fluorouracil (PF) along with interferon-alpha2b and concurrent chemoradiation offers superior loco-regional control for locally advanced carcinoma of oral tongue.Aims:The study was designed to evaluate the beneficial role of induction PF chemotherapy and interferon-alpha2b followed by chemoradiation over definitive chemoradiation only for patients with locally advanced carcinoma of oral tongue.Settings and Design:Phase II randomized, prospective, open-labeled, single-institutional study.Methods and Material:Fifty patients were randomized into 2 arms. Arm A patients were treated with induction chemotherapy with PF regimen for 3 cycles and interferon alpha 2b, 3MU biweekly for 6 such followed by chemoradiation with cisplatin 30 mg/ m2/ week and external radiotherapy. Arm B patients received chemoradiation only, in the same dose schedule as in Arm A. Statistical analysis used: Chi-square test was done to find out the statistical correlation between the two arms. For plotting the disease-free survival (DFS) and overall survival (OS) for the two arms, Kaplan-Meier method was used.Results:The loco-regional response rate of patients treated with interferon containing induction chemotherapy followed by concurrent chemoradiation was superior to concurrent chemoradiation only. However the toxicities and treatment interruption were more in patients treated with induction chemotherapy.Conclusions:In locally advanced carcinoma of oral tongue, induction chemotherapy with cisplatin and 5-fluorouracil (PF) along with interferon alpha 2b followed by concurrent chemoradiation may produce superior loco-regional control with manageable toxicities that needs to be validated by more randomized trials with adequate number of patients.

Concurrent Chemoradiation with Weekly Gemcitabine and Cisplatin in Locally Advanced Carcinoma of the Head and Neck

ABSTRACT Aim: To assess immediate locoregional response to concurrent chemoradiation with gemcitabine and cisplatin in locally advanced head and neck cancer and to assess the toxicity. Methods: 30 patients of stage 3 and 4 squamous cell carcinoma of head and neck were taken for this single arm prospective study .They were treated with gemcitabine 20mg/m2 and cisplatin 30mg/m2 once a week, concurrent with radiotherapy in a conventional fractionated manner of 2Gy per fraction, up to a total of 70Gy, 5 days a week, completed in 7 weeks. The response to treatment and acute toxicity were assessed clinically, during treatment and after 4-6 weeks of treatment. Toxicities were graded using RTOG acute morbidity criteria and CTCAE criteria. Results: The complete and partial response rates were 80% and 20%, respectively. 46% had grade 1 haematological toxicity. No renal toxicity was seen. 73.3% had grade 3 mucositis, 16% from grade 2. 36.6% showed grade 3 skin reaction. Compared with concurrent chemoradiation with weekly cisplatin, this study showed an increase in complete response (80% vs 60%), but an increase in mucosal toxicity was also seen, which was statistically significant. Conclusions: Concurrent chemoradiation with weekly gemcitabine and cisplatin shows promising results with slightly high but manageable toxicity. However, randomized trials are needed in future to further validate this regimen. Disclosure: All authors have declared no conflicts of interest.

Concomitant Chemoradiation versus Accelerated Radiotherapy in Selected Cases of Locally Advanced Carcinoma Cervix – A Prospective Study

Introduction : Although concomitant chemoradiation (CTRT) is the standard of care for locally advanced cervical cancer (LACaCx), it cannot be administered safely in elderly patients or those with certain comorbidities. Aims: To evaluate the feasibility and efficacy of six fractions per week of pure accelerated external beam radiotherapy (EBRT) with standard CTRT, for selected patients with LACaCx. Materials and Methods: From January - September 2010, 45 patients with LACaCx (FIGO stage II B - III B) were administered EBRT 50 Gy / 25 fractions as: 21 in Arm A - Six fractions per week pure accelerated EBRT without chemotherapy and 24 in Arm B - Five fractions per week of conventional CTRT. Patients in both arms received identical brachytherapy. Continuous variables, means-medians were compared with unpaired 't' test and categorical data were compared with 'chi square' test. Disease Free Survival (DFS) was assessed using Kaplan Meier curves. Results: Treatment Time was significantly lesser in Arm A (p< 0.0001) with lesser gaps during radiation (p = 0.0156). Overall responses were comparable at the end of treatment and last follow up (median 37 months). Acute toxicities were higher in Arm B with significantly lesser average number of adverse events (AEs) in Arm A (All Grades: p = 0.0178 and Grade ≥ 3 : p = 0.0314). Late toxicities, 3 year locoregional response and median DFS were similar. Conclusion: The results of our study indicate that pure accelerated EBRT alone may be an effective and feasible alternative to CTRT in certain patients with LACaCx.

Evaluation of Protracted Cisplatinum Infusion in Advanced Anaplastic Thyroid Cancer

Introduction: Anaplastic thyroid cancer (ATC) constitutes 1-3% of all thyroid malignancies. Most of the patients of anaplastic thyroid cancer presents with advanced inoperable lesion associated with neck mass dysphagia, and SVC syndrome. At this stage only treatment that can be offered is chemotherapy, as this variety of thyroid cancer does not generally concentrate iodine. Present study evaluates protracted (8 hr) Cisplatinum (CDDP) infusion along with doxorubucin in comparison to conventional (1hr) Cisplatinum + doxorubucin in advanced anaplastic thyroid cancer in terms of tolerance, toxicities and response rates. Methods: 32 previously untreated cases of stage III/IV inoperable anaplastic thyroid cancer were included in the present study. Patients were divided into 2 arms of 16 patients each. Arm I (16 patients) received 1 hr Cisplatin (CDDP) infusion 75mg/m2 + Doxorubicin 60mg/m2 infusion & Arm II (16 patients) received protracted 8 hrs CDDP infusion 75mg/m2+ Doxorubicin 60mg/m2 infusion. All patients were evaluated for tolerance, toxicities and response rate. Results: Arm II patients showed better locoregional response with CR 31.25%, PR 50%, SD 6.25%,PrD. 12.5% as compared to Arm I patients with CR 12.5%, PR 43.75%, SD 18.75%, Pr. D 25%, p= .02. Toxicities like mucositis, nausea & vomiting, diarrhea, nephrotoxicity were also significantly less in Arm II. After completion of 3-4cycles of Induction CT, all patients were treated with External Radiotherapy of 60-66Gy, followed with 2-3 cycles of adjuvant CT. Conclusion: From the present study it can be concluded that protracted cisplatinum infusion along with other chemotherapeutic drugs is an effective and acceptable CT regimen in advanced inoperable thyroid cancer.