Concomitant Platinum-based Chemotherapy Research Articles

Impact of low skeletal muscle mass in oropharyngeal cancer patients treated with radical chemo-radiotherapy: A mono-institutional experience.

Low skeletal muscle mass index (SMI) has recently emerged as an independent prognostic factor in oncological patients and it is linked with poor survival and higher treatment toxicity. The present study aims to determine the possible impact of low SMI on survival and acute toxicity in oropharyngeal patients. Seventy-six patients with locally advanced oropharyngeal squamous cell carcinoma (stage III-IVC) were treated in our institution with Helical TomoTherapy® (HT - Accuray, Maddison, WI, USA) between 2005 and 2021. All patients received concomitant platinum-based chemotherapy (CT) (at least 200 mg/m2). The SMI was determined using the calculation of cross-sectional area at C3. Twenty patients (26%) presented pre-treatment low SMI, according to Chargi definitions. All patients concluded the treatment. Thirteen patients with low SMI (65%) and 22 patients with normal SMI (39%) presented acute toxicity greater than or equal to grade 3, but this difference was not statistically significant (p-value = 0.25). Overall survival was analyzed in 65 patients, excluding those who finished CT-RT less than six months before the analysis. Overall survival was significantly lower in low SMI versus normal SMI patients (p-value = 0.035). Same difference was observed in N0-N2a patients, suggesting an important role of SMI also in lower nodal burden and putatively better prognosis. Although the results are limited to a small population, our case series has the advantage to be very homogeneous in patients and treatment characteristics. In our setting, SMI demonstrated a crucial impact on overall survival. Further investigation with larger samples is necessary to confirm our results to improve patient outcomes.

Real world data on off-label use of consolidation durvalumab in newly diagnosed stage II and recurrent non-small cell lung cancer patients treated with definitive chemoradiotherapy.

e18857 Background: Consolidation durvalumab is approved for treatment of newly diagnosed, unresectable stage III non-small cell lung cancer (NSCLC) who have not progressed after definitive chemoradiotherapy (CRT) and the NCCN guidelines has since included stage II NSCLC who have not progressed after definitive CRT. Methods: A retrospective, observational real-world study was conducted to identify and describe the off-label use of consolidation durvalumab in NSCLC after completion of CRT between June 2018-June 2021. Data sources included claims data and electronic medical records submitted with prior authorization (PA) requests to OncoHealth, a digital health company that reviews PA requests for cancer treatment. With a data cut-off of 12/22/2022, real-world Time to Progression (rwTTP) and real-world Time to Next Treatment (rwTTNT) were evaluated. All endpoints were measured from the start of consolidation durvalumab treatment; rwTTP spanned until earliest date of clinician-reported progression and rwTTNT spanned until initiation of subsequent treatment. Results: Among 326 patients identified to have received durvalumab after definitive CRT, 45 (13.8%) received off-label treatment. The median age was 71 years (range: 53 to 88), 51% male, 53% former smokers, 29% Stage I, IIA or IIB, 71% locoregional recurrent disease; 58% squamous histology, 47% had undergone prior surgery +/- adjuvant chemo, 27% received prior radiation only and 98% received concomitant platinum-based chemotherapy prior to durvalumab. Median time to initiating durvalumab after CRT was 47 days. After a median follow up of 13.1 (range: 7.0-50.7) months, 33% (n = 15) had progression of disease. The median rwTTP was 14.0 (range: 4.2-32.9) months and median rwTTNT was 14.7 (range: 6.0-33.0) months. Conclusions: In the real world, off-label use of consolidation durvalumab was based on clinical justification and extrapolation of results from PACIFIC trial. The results of rwTTP and rwTTNT outcomes suggest patients with early stage or recurrent disease achieved clinically meaningful benefit from treatment approach used in the PACIFIC trial. With additional patients and longer follow up, real-world data could shed light on the appropriateness of expanding off-label use of durvalumab consolidation.

Real world assessment of clinical benefit with consolidation durvalumab following chemoradiotherapy in stage III unresectable non-small cell lung cancer.

e18853 Background: The phase III PACIFIC trial compared the efficacy of consolidation durvalumab to placebo in newly diagnosed, unresectable stage III non-small cell lung cancer (NSCLC) who had not progressed after chemoradiotherapy (CRT). With a median follow-up of 34.2 months, the median progression free survival (PFS) was 16.9 months (13.0-23.9) compared to 5.6 months (4.6-7.7) for placebo (HR = 0.55, 95% CI,0.45-0.68). We report a real-world study that utilizes surrogate endpoints to assess duration of clinical benefit with consolidation durvalumab. Methods: OncoHealth, a digital health company, conducted a retrospective observational real-world study to assess time to treatment failure in patients with unresectable Stage III NSCLC who received consolidation durvalumab after completion of CRT between June 2018-June 2021. Data sources included electronic medical records (EMR) submitted with prior authorization (PA) requests to OncoHealth and medical claims data. With a data cut-off of 12/22/2022, real-world Time to Progression (rwTTP), and real-world Time to Next Treatment (rwTTNT) were evaluated to assess time to treatment failure. All end points were measured from durvalumab administration dates, rwTTP spanned until earliest date of clinician-assessed progression, and rwTTNT spanned until initiation of subsequent treatment. Results: Total of 281 patients with unresectable Stage III NSCLC who received durvalumab after completion of definitive CRT were identified. Median age was 71 years (range: 53 to 88), 57% male, 53% former smokers, 47% Stage IIIA, 52% non-squamous histology and 98% received concomitant platinum-based chemotherapy prior to durvalumab. Median time between completing CRT and initiating durvalumab was 41 days. With a cutoff date of 12/22/2022, and a median follow up of 28.4 months, 34% (n = 95) experienced disease progression. Sites of progression included lung, lymph nodes, adrenal, liver, bone and brain. The median rwTTP was 10.6 months (range: 2.0-38.1 months) and median rwTTNT was 12.4 months (range: 2.5-39.6 months). Conclusions: In this real-world study, the patient and disease characteristics available in EMR were comparable to those reported in the PACIFIC trial. The rwTTP and rwTTNT reported here suggest treatment failure occurred within one year of exposure to durvalumab and subsequent line of treatment was initiated shortly thereafter. Variables such as co-morbidities, performance status, treatment compliance, change of payers and barriers to treatment in real world will be further explored.

Image-guided adaptive brachytherapy for advanced cervical cancer spreading to the bladder and/or rectum: Clinical outcome and prognostic factors

IntroductionRefinements of brachytherapy techniques have led to better local control of locally advanced cervical cancer (LACC), especially with the development of image-guided adaptive brachytherapy (IGABT). Data on the efficacy of brachytherapy in cervical cancer spreading to adjacent organs are scarce. We report the experience of our institution in the treatment of these advanced tumors with IGABT. Materials and methodsMedical records of patients treated for a LACC spreading to the bladder and/or rectum between 2006 and 2020 at Gustave Roussy Institute were analyzed. Dosimetric parameters were collected and converted into 2 Gy per fraction equivalent doses, including the minimal dose received by 90% of the high-risk target volume (D90 CTVHR) and intermediate-risk target volume (D90 CTVIR), as well as the dose received by the most exposed 2 cm3 of the organs at risk. A Cox regression model was used to study the potential associations between clinical and dosimetric factors with survival endpoints and fistula formation. Results and statistical analysisA total of 81 patients were identified. All patients received pelvic+/− para-aortic radiotherapy, 45 Gy in 25 fractions +/− boost to gross lymph nodes. Concomitant platinum-based chemotherapy was administered in 93.8% of cases. The median D90 CTVHR dose was 75.5 GyEQD2 (SD: 10.39 GyEQD2) and median CTVHR volume was 47.6 cm3 (SD: 27.9 cm3). Median bladder and rectal D2cm3 dose were 75.04 GyEQD2 (SD: 8.72 GyEQD2) and 64.07 GyEQD2 (SD: 6.68 GyEQD2). After a median follow-up of 27.62 ± 25.10 months, recurrence was found in 34/81 patients (42%). Metastatic failure was the most common pattern of relapse (n = 25). Use of a combined interstitial/intracavitary technique and D90 CTVHR ≥ 75.1 GyEQD2 were prognostic factors for OS in univariate analysis (HR = 0.24, 95%IC: 0.057–1, p = 0.023; HR = 0.2, 95%IC: 0.059–0.68, p = 0.0025, respectively). In multivariate analysis, a D90 CTVHR ≥ 75.1 GyEQD2 was significant for OS (HR = 0.23; 95%IC: 0.07, 0.78, p = 0.018). The occurrence of vesicovaginal fistula (VVF) was the most frequent pattern of local recurrence (HR = 4.6, 95%CI: 1.5–14, p = 0.01). ConclusionAdvances in brachytherapy modalities improved local control and survival while reducing toxicities. Enhancing local control through dose escalation and combined intracavitary/interstitial brachytherapy techniques is a major factor in patients cure probability, together with systemic intensification to better control distant events.

Prevention and management of cetuximab-related hypomagnesemia.

321 Background: Cetuximab is an epidermal growth factor receptor monoclonal antibody indicated for the treatment of squamous cell carcinoma of the head and neck and RAS wild-type metastatic colorectal cancer. Hypomagnesemia is a reversible adverse event associated with cetuximab treatment. Here, we provide the key considerations in prevention and management of cetuximab-related hypomagnesemia events in clinical practice. Methods: A PubMed literature search was conducted for articles published between 18 March 2012 and 18 March 2022 using “cetuximab” and “hypomagnesemia” as keywords. Of the 75 articles retrieved, 20 were considered relevant and are included here.Articles were excluded if they focused on hypomagnesemia-associated clinical benefits. Data were summarized and grouped into the following categories: risk and risk factors; monitoring; prevention; and management. Results: The relative risk of grade 3/4 hypomagnesemia following cetuximab therapy appears to be approximately 1.5 times higher for colorectal cancer compared with head and neck cancer. Several risk factors have been identified including age, comorbidities, treatment duration, baseline electrolyte levels, concomitant platinum-based chemotherapy, and polypharmacy. Although the frequencies of hypomagnesemia events vary between the studies identified, data from the included meta-analyses suggest that the incidence of grade 3/4 hypomagnesemia is around 4% among patients receiving cetuximab therapy. Early and regular monitoring of magnesium levels is recommended ideally every 4 to 8 weeks, especially in patients at high risk of serious complications, and up to 8 weeks following treatment cessation. Proposed proactive prophylactic interventions include magnesium supplementation for patients with baseline magnesium levels < 1.8 mg/dL, to prevent severe hypomagnesemia. The management approach depends on the degree of hypomagnesemia, the symptoms and risk factors, and may include supplementation with oral magnesium salts and/or parenteral forms; intravenous forms may be preferred due to low bioavailability and gastrointestinal adverse events related to oral supplements. While recommendations for initiating magnesium replacement in grade 1 (> 1.2 mg/dL) and grade 2 (0.9–1.2 mg/dL) hypomagnesemia events vary, magnesium supplementation should be given to patients with grade 3 (0.7–0.9 mg/dL) or grade 4 (< 0.7 mg/dL) hypomagnesemia, due to high risk of serious adverse cardiac events. If magnesium levels do not improve or continue to decrease despite supplementation, a pause in cetuximab administration may be considered. Conclusions: Hypomagnesemia is a reversible and manageable cetuximab-related adverse event and should not interfere with treatment outcomes. A periodic check of magnesium levels during treatment with cetuximab is recommended.

Radical Radiotherapy of Locally Advanced Cervix Uteri Carcinoma

External beam radiotherapy with concomitant platinum-based chemotherapy followed by brachytherapy is defined as radical radiotherapy of cervix uteri carcinoma. Radical radiotherapy is the gold standard treatment for locally advanced cervix uteri carcinoma

Cochlea sparing optimized radiotherapy for nasopharyngeal carcinoma

BackgroundDefinitive chemoradiotherapy (CRT) is standard of care for nasopharyngeal carcinoma. Due to the tumor localization and concomitant platinum-based chemotherapy, hearing impairment is a frequent complication, without defined dose-threshold. In this study, we aimed to achieve the maximum possible cochleae sparing.Materials and methodsTreatment plans of 20 patients, treated with CRT (6 IMRT and 14 VMAT) based on the QUANTEC organs-at-risk constraints were investigated. The cochleae were re-delineated independently by two radiation oncologists, whereas target volumes and other organs at risk (OARs) were not changed. The initial plans, aiming to a mean cochlea dose < 45 Gy, were re-optimized with VMAT, using 2–2.5 arcs without compromising the dose coverage of the target volume. Mean cochlea dose, PTV coverage, Homogeneity Index, Conformity Index and dose to other OAR were compared to the reference plans. Wilcoxon signed-rank test was used to evaluate differences, a p value < 0.05 was considered significant.ResultsThe re-optimized plans achieved a statistically significant lower dose for both cochleae (median dose for left and right 14.97 Gy and 18.47 Gy vs. 24.09 Gy and 26.05 Gy respectively, p < 0.001) compared to the reference plans, without compromising other plan quality parameters. The median NTCP for tinnitus of the most exposed sites was 11.3% (range 3.52–91.1%) for the original plans, compared to 4.60% (range 1.46–90.1%) for the re-optimized plans (p < 0.001). For hearing loss, the median NTCP of the most exposed sites could be improved from 0.03% (range 0–99.0%) to 0.00% (range 0–98.5%, p < 0.001).ConclusionsA significantly improved cochlea sparing beyond current QUANTEC constraints is feasible without compromising the PTV dose coverage in nasopharyngeal carcinoma patients treated with VMAT. As there appears to be no threshold for hearing toxicity after CRT, this should be considered for future treatment planning.

A rare case report of sinonasal undifferentiated carcinoma of paranasal sinuses

&lt;p&gt;Sino nasal malignancies account for only 0.2-0.8% of all malignancies and undifferentiated carcinoma is rare malignant tumour of sinonasal tract, with extremely poor prognosis. We report a case of sinonasal undifferentiated carcinoma which we managed by surgery followed by post-operative radiotherapy with concomitant platinum-based chemotherapy. Although the overall survival is about 20% at 5 years and there are frequent recurrences combined modality treatment is the best management option available at present.&lt;/p&gt;

Propensity score matching analysis of patients with inoperable stage III NSCLC treated with chemoradio- vs. chemoradioimmunotherapy.

e21087 Background: Chemoradiotherapy (CRT) followed by consolidation treatment with the PD-L1 Inhibitor durvalumab is the new standard of care for inoperable stage III NSCLC. The present study compares outcome of patients treated with CRT alone to those treated with additional concurrent and/or sequential immune check-point inhibition (CRT-IO) using propensity-score matching analysis (PSM). Methods: PSM was performed with retro- and prospectively collected data of patients treated with CRT or CRT-IO (consolidation with durvalumab/concurrent and consolidation with nivolumab). Overall survival (OS), progression free survival (PFS) and time to loco-regional recurrence (defined as progression in the mediastinum and ipsilateral lung) were calculated from last day of thoracic irradiation. Results: Sixty-two (37%) of 166 treated patients were successfully matched; 31 received CRT and 31 CRT-IO. 18F-FDG-PET/CT for treatment planning was performed in 97% and cranial contrast enhanced MRI in 81% of patients. PSM was based on age, gender, PTV volume, histology, T- and N-stage. 36 and 51% vs. 42 and 46% of patients had T4- and N3-disease in the CRT and CRT-IO cohorts, respectively. All patients were irradiated to a total dose of at least 60Gy (EQD2). 90% of patients received two cycles of concomitant platinum-based chemotherapy (CRT: 82%, CRT-IO 96%). The median follow-up for 62 patients was 17.3 (range: 1.7-96.0) months. Median PFS was 7.1 (95%CI 2.2-12.1) months in CRT vs. 13.8 (95%CI 13.1-14.5) in CRT-IO patients (p = 0.004). Twelve-month PFS rates were 30% and 55% in the CRT and the CRT-ICI cohort, respectively. Median time to loco-regional recurrence was 15.3 months for CRT vs. not reached for CRT-IO patients (p = 0.050). 12-month loco-regional recurrence rates were 43% vs. 22%; 6- and 12-month brain metastases rates after completion of radiotherapy in the CRT vs. CRT-ICI cohort were 8% and 26% vs. 0% and 20%, respectively. Median OS was 19.1 (8.4-29.8 95%CI) months for CRT and not reached for CRT-IO patients (p &lt; 0.001). 12-month survival rates were 62% and 93% in the CRT and CRT-IO cohort, respectively. Conclusions: The addition of concurrent and/or sequential IO to CRT led to an impressive improvement of loco-regional control, PFS and OS in the matching cohorts.

Prognostic value of the TGFß1 rs4803455 single nucleotide polymorphism and its association with prophylactic cranial irradiation in small cell lung cancer.

e21038 Background: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single-nucleotide polymorphisms (SNP) in Heat shock protein beta- 1 (HSPB1) and Transforming growth factor (TGFß1) and survival have been investigated. Methods: A prospective multicenter study of 94 SCLC patients treated between 2013 and 2016 was conducted. Several variables clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFß1 gene and 5 of HSPB1 gene) variables were analyzed. Results: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (BID in 42%). Forty-seven percent received concomitant platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis PCI and the TGFß1 SNP rs4803455 showed a statistically significant association with OS and local control. Patients with the CA genotype of the TGFß1 SNP rs4803455 showed worse OS (HR 2.53; IC 1.22-5.21; p = 0.012) and higher local recurrence (HR 2.26; IC 1.01-5.08;p = 0.048). A combined analysis showed that those patients receiving PCI and carrying the rs4803455:CA genotype had a statistically significant lower OS (p &lt; 0.001) and disease-free survival (p &lt; 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. Conclusions: Genetic analysis showed that the CA genotype of TGFß1 SNP rs4803455 was associated with worse prognosis in SCLC patients and could be considered as a potential biomarker for OS.

Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer

Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 μg (n = 56), 100 μg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.

Long-Term Experience of Chemoradiotherapy Combined with Deep Regional Hyperthermia for Organ Preservation in High-Risk Bladder Cancer (Ta, Tis, T1, T2).

The aim of this study was to evaluate the efficacy and safety of chemoradiotherapy (RCT) combined with regional deep hyperthermia (RHT) of high-risk bladder cancer after transurethral resection of bladder tumor (TUR-BT). Between 1982 and 2016, 369 patients with pTa, pTis, pT1, and pT2 cN0-1 cM0 bladder cancer were treated with a multimodal treatment after TUR-BT. All patients received radiotherapy (RT) of the bladder and regional lymph nodes. RCT was administered to 215 patients, RCT + RHT was administered to 79 patients, and RT was used in 75 patients. Treatment response was evaluated 4-6 weeks after treatment with TUR-BT. Complete response (CR) overall was 83% (290/351), and in treatment groups was RT 68% (45/66), RCT 86% (178/208), and RCT + RHT 87% (67/77). CR was significantly improved by concurrent RCT compared with RT (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.05-5.12; p = .037), less influenced by hyperthermia (OR, 2.56; 95% CI, 0.88-8.00; p = .092). Overall survival (OS) after RCT was superior to RT (hazard ratio [HR], 0.7; 95% CI, 0.50-0.99; p = .045). Five-year OS from unadjusted Kaplan-Meier estimates was RCT 64% versus RT 45%. Additional RHT increased 5-year OS to 87% (HR, 0.32; 95% CI, 0.18-0.58; p = .0001). RCT + RHT compared with RCT showed a significantly better bladder-preservation rate (HR, 0.13; 95% CI, 0.03-0.56; p = .006). Median follow-up was 71 months. The median number of RHT sessions was five. The multimodal treatment consisted of a maximal TUR-BT followed by RT; concomitant platinum-based chemotherapy combined with RHT in patients with high-grade bladder cancer improves local control, bladder-preservation rate, and OS. It offers a promising alternative to surgical therapies like radical cystectomy. Radical cystectomy with appropriate lymph node dissection has long represented the standard of care for muscle-invasive bladder cancer in medically fit patients, despite many centers reporting excellent long-term results for bladder preserving strategies. This retrospective analysis compares different therapeutic modalities in bladder-preservation therapy. The results of this study show that multimodal treatment consisting of maximal transurethral resection of bladder tumor followed by radiotherapy, concomitant platinum-based chemotherapy combined with regional deep hyperthermia in patients with Ta, Tis, T1-2 bladder carcinomas improves local control, bladder-preservation rate, and survival. More importantly, these findings offer a promising alternative to surgical therapies like radical cystectomy. The authors hope that, in the future, closer collaboration between urologists and radiotherapists will further improve treatments and therapies for the benefit of patients.

Toxicity Reduction in the Treatment of HPV Positive Oropharyngeal Cancer: Emerging Combined Modality Approaches.

Human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) is a distinct clinical entity within the head and neck cancers, with a unique epidemiology and, in general, a favorable prognosis. Because of this favorable prognosis, researchers have considered de-intensifying the current standard treatment of HPV+ OPC in order to reduce acute and late treatment related toxicity without compromising outcome. Current ongoing trials can be divided in three main categories: de-intensification of the chemotherapy by replacing concomitant platinum-based chemotherapy with the EGFR-inhibitor cetuximab, or de-intensification of the radiation dose of either the primary radiotherapy of selected, good-responding patients after induction chemotherapy or of the adjuvant radiotherapy based on pathology features after primary surgery. Despite the good prognosis of the majority of HPV+ OPC patients, a proportion of them still have poor prognosis. This unmet need has led clinical research on new treatment strategies focused on influencing the unique micro-environment of HPV+ OPC with for example immunotherapy. This article summarizes the current understanding regarding the optimal treatment of non-metastatic HPV+ OPC. Ongoing and published clinical trials regarding de-intensification strategies, immunotherapy and proton therapy are described focusing on the rationale and underlying evidence of these emerging treatment strategies. Nevertheless, until the results of the ongoing trials are known, the treatment of HPV+ OPC in clinical practice should remain identical to the treatment of HPV negative OPC.

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer.

The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC). 21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded. The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: Dmax, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6-33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%. SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine. Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification.

Definitive chemoradiotherapy for advanced cervical cancer: should it be different in the elderly?

BackgroundCervical cancer (CC) is the second most common cancer in Brazilian women, and approximately 10% of cases occur in elderly patients (pts). In this age group, disease is usually diagnosed in more advanced stages and oncological therapies are usually less intensive, due to comorbidities and impaired performance status. MethodsRetrospective analysis of pts ≥65 years old with CC admitted at a Brazilian University Cancer Center from August 2008 to February 2012. We performed a descriptive analysis of baseline performance status (PS), disease stage (FIGO), histology, body mass index (BMI), treatment received and overall survival, using the Kaplan–Meier method. Results900 medical records were analyzed and 75 pts (8%) fulfilled the inclusion criteria. Median age was 73.4 years old (±5.5 years). Squamous cell carcinoma (SCC) was the most common histology (71 pts, 94.7%). 67 (89.3%) had PS 0 or 1 and 52 pts (69.3%) were eutrophic (BMI 18.5–25kg/m2). At presentation, disease staging consisted of 18 pts (24%) stage I, 35 pts (46.7%) stage II, 8 pts (10.7%) stage III, 12 pts (16%) stage IVa and 2 pts (2.7%) stage IVb. 24 pts (32%) underwent surgery (hysterectomy, adnexectomy, pelvic and paraaortic lymphadenectomy). Adjuvant treatment with radiotherapy (RT) was performed in 13 pts (total dose of external RT in pelvis ranged from 39.6 to 45Gy, parametrial boost ranged from 14 to 20Gy and 4 inserts from 7 to 7.5Gy of brachytherapy); 8 of them received concomitant platinum-based chemotherapy (CT). 30 pts underwent definitive CRT, 17 definitive RT, 1 palliative CT and 3 best supportive care. In the CRT group, 18 pts received cisplatin (CDDP 40mg/m2/w/6w) and 12 carboplatin (AUC 2/w/6w). During definitive CRT, treatment was discontinued in 39% of pts who received CDDP and 25% of pts who received carboplatin, all due to treatment toxicities. CDDP was associated with more nefrotoxicity (5 pts, 28%) than carboplatin (1 pt, 8.3%). The CDDP group also presented more radiodermatitis and stroke. However, myelosuppression and diarrhea were similar in both groups. After a 26.1-month follow-up, median OS was not reached. ConclusionsDespite advanced age, more than 60% of pts underwent complete CRT treatment. Thus, age should not be the only factor to guide therapeutic decisions in CC. Carboplatin was better tolerated than CDDP in CRT group, but prospective trials are necessary to evaluate the best treatment option in this population.

Phase II/III randomized study of hyperfractionated radiotherapy with concomitant cetuximab versus concomitant platinum-based chemotherapy in advanced non-metastatic head and neck cancer: Update.

e17044 Background: This is an update of a randomized study comparing the use of cetuximab versus platinum based chemotherapy with concurrent hyperfractionated radiation therapy (HRT) in locally adv...

Palmar Bullous Blistering Induced by Erlotinib

A 56-year-old female was allocated to definite radiotherapy of 66 Gy (5 weekly fractions of 2 Gy) because of stage III non-small cell lung cancer (T1bN3M0, middle-differentiated adenocarcinoma). Epidermal growth factor receptor (EGFR) mutation test was negative. Standard concomitant platinumbased chemotherapy was avoided because of a chronic kidney disease. As an alternative, concomitant erlotinib 150 mg once a day was prescribed based on the possible radiosensitizing effect by targeting the EGFR, even in the absence of EGFR mutation.1 After a few days, she developed mild acneiform facial rash and mild diarrhea. Twenty-three days after the start of the treatment, she noticed a small blister in one of her palms. A severe skin reaction developed rapidly within the next 2 days and included painful hemorrhagic palmar bullae (Figure 1), maculopapular

Neck Dissection can be avoided after Sequential Chemoradiotherapy and Negative Post-treatment Positron Emission Tomography-Computed Tomography in N2 Head and Neck Squamous Cell Carcinoma

Aims This study assessed neck control in patients with N2 head and neck squamous cell carcinoma (HNSCC) treated with sequential chemoradiotherapy (SCRT) and the incidence of neck recurrence when neck dissection was withheld in those with negative post-treatment fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Materials and methods Thirty-four consecutive patients with N2 HNSCC who were treated with radical intent using SCRT were included. Twenty-seven patients received concomitant platinum-based chemotherapy with their radiotherapy. Nineteen patients were treated with intensity-modulated radiotherapy. PET-computed tomography (PET-CT) was obtained 3 months after the completion of radical radiotherapy. Neck dissection was carried out only in those with increased FDG uptake in the neck. Results The median follow-up was 39.1 months. One patient had increased FDG uptake in the neck post-treatment, which was false positive for malignancy. The remaining 33 patients were observed without neck dissection. No regional recurrence occurred. The negative predictive value (NPV) of post-treatment PET-CT was 100%. Conclusions Good disease control in the neck can be achieved in patients with N2 HNSCC with SCRT. Post-treatment PET-CT has a high NPV. Neck dissection can be avoided if post-treatment PET-CT is negative.

Biologics in Cervical Cancer Therapy

Though cervical cancer incidence and prevalence have decreased in the United States, the disease remains a very important cause of morbidity and mortality worldwide. Current therapy for early-stage disease is surgical with adjuvant therapy being administered according to histopathologic findings. Pelvic radiation with concomitant platinum-based chemotherapy is used to treat locally advanced disease, whereas metastatic and recurrent lesions continue to be difficult to effectively treat and cure. Clinical trials in this latter scenario have suggested that clinical benefit may be associated with biologic therapies. This article focuses on the use of targeted therapies in cervical cancer, specifically evaluating antiangiogenesis and endothelial growth factor receptor-related treatments.

Impact of NCI Clinical Announcement upon use of chemoradiation for women with cervical cancer

5537 Background: On the basis of 5 NCI-sponsored randomized phase III trials, in 1999 the NCI issued a Clinical Announcement recommending that women with cervical cancer who require radiation also receive concomitant platinum-based chemotherapy. We undertook a population-based cohort study to determine whether the 1999 NCI Clinical Announcement was associated with changes in clinical practice in the United States. Methods: Through the NCI’s SEER program, we identified 973 women with invasive cervical cancer diagnosed in 1997, 773 diagnosed in 2000, and 1370 diagnosed in 2001. Hospital records were re-abstracted and treated physicians were contacted to verify initial therapy provided to each patient. Results: In multivariate analysis, we found a significant increase in the use of chemoradiation between 1997 and 2001/2001 among women with cervical cancer of all stages for which radiation would be appropriate. (see table ). Compared to women with well-differentiated tumors, women with moderately or poorly differentiated tumors were more likely to receive chemoradiation. Women aged 75 years or older were significantly less likely to receive chemoradiation than younger women. We saw no impact of race/ ethnicity or insurance status upon receipt of chemoradiation. Conclusions: Publication of the results from these 5 sutdies, extensive professional educational efforts, and the NCI’s Clinical Announcement were associated with widespread adoption of chemotherapy in the treatment of cervical cancer in the United States. [Table: see text] No significant financial relationships to disclose.