Induction Concurrent Chemoradiotherapy Research Articles

Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer

BackgroundLung cancer is associated with a high mortality rate worldwide. Non-small-cell lung cancer (NSCLC) is a major subtype of lung cancer. Carboplatin (CBDCA) plus nab-paclitaxel (PTX) has become a standard treatment for advanced unresectable NSCLC. However, treatment with nab-PTX has not been established as a standard therapy for resectable locally advanced (LA)-NSCLC.MethodsWe conducted a comprehensive study involving consecutive patients with locally advanced NSCLC who underwent induction therapy including nab-PTX followed by surgical resection. Fifteen patients with locally advanced NSCLC underwent induction therapy including nab-PTX followed by surgical resection. Concurrent chemoradiotherapy (CRT) consisted of weekly administration of nab-PTX (50 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (50 Gy/25 fractions).ResultsThe clinical stages were as follows: IIB (n =1), IIIA (n =12), and IIIC (n =2). Downstaging was observed in 73% (11/15) of patients on comparison with the clinical stage before concurrent CRT. Adverse drug reactions were observed in seven patients. Complete resection was performed in all patients. The re-evaluated pathological stage after pretreatment was diagnosed as stage 0 in three patients, stage IA1 in six, stage IA2 in one, and stage IIIA in five. The pathological effects of previous therapy were as follows: Ef3 (n =3), Ef2 (n =9), and Ef1a (n =3).ConclusionThe therapeutic effect of induction therapy including nab-PTX was promising. Induction CRT, including nab-PTX, followed by resection, may be a viable alternative treatment option for locally advanced NSCLC.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section.

Superior Sulcus Tumors Invading the Spine: Multimodal Treatment Outcomes From the Preimmunotherapy Era

IntroductionCurative-intent treatment of superior sulcus tumors (SSTs) of the lung invading the spine presents considerable challenges. We retrospectively studied outcomes in a single center, uniformly staged patient cohort treated with induction concurrent chemoradiotherapy followed by surgical resection (trimodality therapy). MethodsAn institutional surgical database from the period between 2002 and 2021 was accessed to identify SSTs in which the resection included removal of at least part of the vertebral body. All patients were staged using fluorodeoxyglucose positron emission tomography (/computed tomography), computed tomography scan of the chest/upper abdomen, and brain imaging. Surgical morbidity was assessed using the Clavien-Dindo classification. Overall and disease-free survival were calculated using the Kaplan-Meier method. ResultsA total of 18 patients were included: 8 complete and 10 partial vertebrectomies were performed, with six of the eight complete vertebrectomies involving two vertebral levels, resulting in Complete surgical resection (R0) in 94%. Nine patients had a 1-day procedure, and nine were staged over 2 days. The median follow-up was 30 months (interquartile range 11–57). The 90-day postoperative morbidity was 44% (grade III/IV), with no 90-day surgery–related mortality. There were 83% who had a major pathologic response, associated with improved survival (p = 0.044). The 5-year overall and disease-free survival were 55% and 40%, respectively. Disease progression occurred in 10 patients, comprising locoregional recurrences in two and distant metastases in eight patients. ConclusionsMultimodality treatment in selected patients with a superior sulcus tumor invading the spine is safe and results in good survival. Such patients should be referred to expert centers. Future research should focus on improving distant control (e.g. [neo]adjuvant immunotherapy).

Dose-volume parameters predict radiation pneumonitis after induction chemoradiotherapy followed by surgery for non-small cell lung cancer: a retrospective analysis

BackgroundThe relationship between lung dose-volume histogram (DVH) parameters and radiation pneumonitis (RP) associated with induction concurrent chemoradiotherapy (CCRT) followed by surgery in patients with non-small cell lung cancer (NSCLC) is unclear, particularly when concerning irradiation of the whole lung prior to resection. We performed this study to identify factors associated with grade ≥ 2 RP in such patients.MethodsPatients who received induction CCRT (chemotherapy: cisplatin and docetaxel; radiotherapy: 46 Gy/23 fractions) between May 2003 and May 2017 were reviewed. The mean lung dose (MLD) and the percentage of the lung volume that received ≥5 Gy (V5) and ≥ 20 Gy (V20) were calculated. Factors associated with the development of grade ≥ 2 RP were analyzed.ResultsOne hundred and eight patients were included in this study, 34 (31.5%) of whom experienced grade ≥ 2 RP. A V20 ≥ 21%, an MLD ≥10 Gy, and a lower lobe tumor location were significant predictors of grade ≥ 2 RP on univariate analysis (p = 0.007, 0.002, and 0.004, respectively). Moreover, an MLD ≥10 Gy and lower lobe location were significant predictors of grade ≥ 2 RP on multivariate analysis (p = 0.026 and 0.0043, respectively). The cumulative incidence rates of grade ≥ 2 RP at 6 months were 15.7 and 45.6% in patients with MLDs < 10 Gy and ≥ 10 Gy, respectively, and were 23.5 and 55.6% in patients with upper/middle lobe- vs. lower lobe-located tumors, respectively.ConclusionsMLD and lower lobe location were predictors of grade ≥ 2 RP in patients who received induction CCRT. It is necessary to reduce the MLD to the greatest extent possible to prevent the occurrence of this adverse event.

Oral vinorelbine plus cisplatin with concomitant radiotherapy as induction therapy for stage III non-small cell lung cancer: Results of a single-arm prospective cohort study.

BackgroundConcurrent chemoradiotherapy (CCRT) is an optimal recommended treatment for stage III non‐small cell lung cancer (NSCLC). Herein, we aimed to investigate the efficacy and safety of oral vinorelbine plus cisplatin with concomitant radiotherapy for stage III NSCLC.MethodsThis prospective, open‐label, single‐arm, observational cohort study was performed between January 2010 and September 2016. Patients were treated with two cycles of chemotherapy with 60 mg/m2 intravenous cisplatin on day 1 and 50 mg/m2 oral vinorelbine on days 1, 8, and 15; radiotherapy was administered concurrently from day 1 when chemotherapy was initiated. A total dose of 66–70 Gy radiotherapy was delivered in daily fractions of 2 Gy for 6.5–7 consecutive weeks. The tumor response was assessed after completing concomitant treatment.ResultsA total of 58 patients were enrolled and analyzed; 31 patients had stage IIIA NSCLC and 27 had stage IIIB NSCLC. After induction CCRT, 31 patients achieved an objective response (complete response in one and partial response in 30; the response rate was 53.4%). The median progression‐free survival was 6.73 months (95% confidence interval [CI], 5.42–7.91), duration of response was 12.30 months (95% CI, 5.59–19.01), and overall survival was 24.83 months (95% CI, 19.26–30.21). No treatment‐related mortality was observed, and neutropenia was the most common grade 3 and 4 treatment‐related toxicity (11 patients; 18.9%).ConclusionsCCRT with the weekly regimen of oral vinorelbine plus triweekly cisplatin was effective and safe for stage III NSCLC.

Phase II study of consolidation amrubicin after concurrent chemoradiotherapy for patients with limited-stage small cell lung cancer.

8555 Background: Concurrent chemoradiotherapy (CCRT) using etoposide and cisplatin has been the gold standard for limited-stage small-cell lung cancer (LS-SCLC) for decades; however, approximately three out of four cases treated by CCRT inevitably relapse. Amrubicin (AMR), a synthetic anthracycline with a structure similar to doxorubicin, has demonstrated strong antitumor activity against relapsed SCLC and has been the standard second-line treatment for SCLC in Japan. We consider consolidation AMR following CCRT to be a potential treatment for patients with LS-SCLC. Methods: In this single-arm, multicenter phase II study, all patients enrolled were treated using induction CCRT consisting of four cycles of etoposide at 100 mg/m2 on days 1-3 and cisplatin at 60 mg/m2 on day 1 every 3 weeks, plus concurrent thoracic radiotherapy (1.5 Gy twice daily, total 45 Gy) concomitant with the first cycle of chemotherapy. Then, eligible patients received three cycles of AMR at 40 mg/m2 on days 1-3 every 3 weeks as consolidation treatment. The primary endpoint was the 2-year progression-free survival (PFS) rate in patients who received consolidation AMR, and the secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), and safety. This study was terminated early due to slow patient accrual. Results: Of the 36 patients who underwent induction CCRT (ITT population), 28 (78%) received AMR as consolidation therapy (consolidation population) and 24 (67%) completed all planned treatments. The 2-year PFS rate and ORR were 35.7% and 86% (8 CR and 16 PR), respectively, in the consolidation population. The median PFS and median OS were 14.3 months (95%CI, 10.8-46.6) and 60.9 months (95%CI, 29.8-NR), respectively, in the consolidation population. In the ITT population, the median PFS and the median OS were 13.4 months (95%CI, 7.5-19.0) and 60.9 months (95%CI, 29.8-NR), respectively. Grade 3/4 toxicities during the consolidation phase included neutropenia (39%), thrombocytopenia (14%), and febrile neutropenia (7%). There were no treatment-related deaths in the ITT population. Conclusions: Consolidation AMR following standard CCRT consisting of etoposide and cisplatin plus concurrent thoracic radiotherapy was feasible, and demonstrated promising efficacy for LS-SCLC. Clinical trial information: 000002352.

Modernes Management des Pancoast-Tumors

ZusammenfassungDer Pancoast-Tumor (Sulcus-superior-Tumor) ist eine Sonderform des Lungenkarzinoms mit Infiltration der oberen Thoraxapertur, die durch Schulterschmerz und eventuell Horner-Syndrom klinisch auffällig wird. Die häufig verspätete Diagnose und die komplexe Anatomie der Region stellen eine Herausforderung für die Therapeuten dar. Dieser Beitrag schildert, wie moderne Diagnostik und multimodale Behandlung die Prognose der Erkrankung positiv beeinflussen können.

Dose-Volume Parameters Predict Radiation Pneumonitis after Surgery with Induction Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer.

To clarify the relationship between dose-volume histogram (DVH) parameters and radiation pneumonitis (RP) after surgery in cases of non-small cell lung cancer (NSCLC) treated with induction concurrent chemoradiotherapy (CCRT). Patients with NSCLC treated with induction CCRT (chemotherapy: cisplatin and docetaxel; radiotherapy: 2.0 Gy fractions once daily for a total of 46 Gy) before surgery were reviewed. We calculated the percentage of lung volume receiving at least 20 Gy (V20) and the mean lung dose (MLD) for the total lung volume and the lung remaining after resection. Factors affecting the incidence of RP at grade 2 or higher (≥ G2 RP) were analyzed. Eighteen of 49 patients (37%) experienced ≥G2 RP. The V20 and MLD for the lung remaining after resection (V20r and MLDr) were significant predictors according to the multivariate analysis (p=0.007 and 0.041, respectively). The incidence of ≥G2 RP was 8% in patients with V20r<10%, and 13% in patients with MLDr<5.6 Gy, respectively. The optimal approach to reduce the rate of postoperative RP in patients with induction CCRT for NSCLC is to keep the V20r below 10% and/or the MLDr below 5.6 Gy in the radiotherapy planning.

Modernes Management des Pancoast-Tumors

Pancoast or superior pulmonary sulcus tumour is a subset of lung carcinoma that invades the structures of the thoracic inlet - first ribs, distal roots of the brachial plexus, stellate ganglion, vertebrae, and subclavian vessels. The first symptom is usually shoulder pain; consequently, most patients are initially treated for osteoarthritis. Late diagnosis is common. Success of therapy depends on an accurate staging: standard imaging with CT scan of the chest, PET-CT scan, brain MRI are needed to rule out distant metastases, endobronchial ultrasound-guided needle biopsy (EBUS-TBNA) or mediastinoscopy are mandatory for reliable nodal staging. An MRI of the thoracic inlet allows to clearly define the boundaries of local invasion. Modern management of Pancoast tumour includes induction concurrent chemoradiotherapy followed by surgical resection. As compared with historical series treated by preoperative radiation, a trimodally approach did enhance complete resection rates and perhaps long-term survival - from about 30% 5-year survival rate to 60% in R0-resected patients. In patients who have unresectable but non-metastatic Pancoast tumours and appropriate performance status, definitive concurrent chemoradiotherapy and radiotherapy are recommended options.

Superior sulcus tumors (Pancoast tumors).

Superior Sulcus Tumors, frequently termed as Pancoast tumors, are a wide range of tumors invading the apical chest wall. Due to its localization in the apex of the lung, with the potential invasion of the lower part of the brachial plexus, first ribs, vertebrae, subclavian vessels or stellate ganglion, the superior sulcus tumors cause characteristic symptoms, like arm or shoulder pain or Horner's syndrome. The management of superior sulcus tumors has dramatically evolved over the past 50 years. Originally deemed universally fatal, in 1956, Shaw and Paulson introduced a new treatment paradigm with combined radiotherapy and surgery ensuring 5-year survival of approximately 30%. During the 1990s, following the need to improve systemic as well as local control, a trimodality approach including induction concurrent chemoradiotherapy followed by surgical resection was introduced, reaching 5-year survival rates up to 44% and becoming the standard of care. Many efforts have been persecuted, also, to obtain higher complete resection rates using appropriate surgical approaches and involving multidisciplinary team including spine surgeon or vascular surgeon. Other potential treatment options are under consideration like prophylactic cranial irradiation or the addition of other chemotherapy agents or biologic agents to the trimodality approach.

Combined treatment modalities in Pancoast tumor: results of a monocentric retrospective study.

A retrospective monocentric study of consecutive patients with superior sulcus tumor non-small cell lung cancer (SS-NSCLC), treated by induction concurrent chemoradiotherapy (CRT), article management. From 1994 to 2005, 36 patients (15 T3, 21 T4 tumors, including N2-N3 node involvement) received induction CRT with cisplatin/vinorelbine/fluorouracil combined with 44 Gy radiotherapy (5 daily 2 Gy fractions/week). After CRT completion, RECIST evaluation and operability were assessed. In resectable patients, surgery was performed one month after CRT. Patients with unresectable disease followed CRT up to 66 Gy. The median of follow-up period was 38.6 months [2-206]. Induction CRT was completed for 94.4% with 71% radiological objective response (OR). Sixteen patients (44%) underwent surgical resection, and pathologic complete resection was performed in 93.8%. There were 7 patients (44%) with pathologic complete response. The median disease-free survival (DFS) time was 12.9 months with DFS rates at 1 and 2 years 53.6% and 39.1% respectively. The median overall survival (OS) was 46.4 months. The OS rates at 2 and 5 years were 68.8% and 37.5% respectively with no difference between T3 and T4 tumors. In unresectable disease, the median DFS time was 8.1 months. The DFS rate at 1 year was 25.2%. The median OS was 9.1 months. The OS rates at 1 and 2 years were 45% and 16.9% respectively. Recurrences were found in 72% of patients. Brain metastasis was the most common site of recurrence. Prognostic factors for OS were the response to induction treatment, the possibility of surgery, and pathologic complete response. This trimodality treatment regimen confers a survival outcome in agreement with previous studies. Patients with pretreatment N3 lymph node should be included in trimodality treatment.

Concurrent Etoposide, Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma, nasal type

PurposeRadiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen. MethodsAn induction phase with two upfront courses of CCRT delivering a 40Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2–3 cycles of ESHAP chemotherapy alone. ResultsThirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3–4 haematological toxicity. The main non-haematological grade 3–4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%. ConclusionsWith optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type.

Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer.

BackgroundAt our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30–40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).Materials and MethodsThrough a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies.ResultsThe intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235–8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054–9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group.ConclusionsCCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival.

Induction of Cd44 Variant 9-Expressing Cancer Stem Cells Attenuates the Efficacy of Chemoradioselection and Worsens the Prognosis of Patients with Advanced Head and Neck Cancer

ABSTRACT Aim: At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chemoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC). Methods: Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies. Results: The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (p = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among 5 candidate factors (T, N, stage, response to CCRT, and CD44v9), CD44v9 positivity alone was significantly correlated with the poor prognosis (HR: 3.140, 95% CI: 1.230-8.017, p = 0.0167). Furthermore, the survival rate of the CD44v9-induced group was significantly (p = 0.04) worse than the CD44v9-non-induced group. Conclusions: CRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. The addition of an xCT (a coupling molecule of CD44v9) inhibitor (e.g., sulfasalazine) to chemoradioselection may provide a new approach for clinically feasible CSC-targeted therapy in HNSCC, improving the efficacy of chemoradioselection and consequent organ preservation and survival. Disclosure: All authors have declared no conflicts of interest.

Predictive value of restaging after induction concurrent chemoradiotherapy for locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction

Background: Current treatment protocols for locoregionally advanced esophageal cancer add concurrent chemoradiotherapy to surgical resection in an effort to improve curative potential. These approaches are intensive and toxic. This retrospective review was undertaken to identify clinical features after concurrent chemoradiotherapy that might predict for treatment failure. Methods: 155 patients with locoregionally advanced adenocarcinoma of the esophagus/gastroesophageal junction were treated with concurrent chemoradiation with 96 hour infusions of cisplatin (20mg/m 2 /day) and fluorouracil (1,000mg/m 2 /day) beginning on day 1 of radiation (30 Gy @ 1.5 Gy bid). Surgery followed in 4-6 weeks with identical concurrent chemotherapy planned post-operatively. 75 patients also received 2 years of oral gefitinib Pretreatment staging evaluation was obtained in all patients which included a medical history, physical examination, complete blood count, serum chemistries, chest radiograph, computed tomographic scans of the chest and abdomen, pulmonary function studies, esophagogastroduodenoscopy (EGD) with biopsy, endoscopic ultrasound (EUS), and bronchoscopy if indicated by symptomatology, or by the extent or location of the primary lesion. This also included assessment of symptomatic dysphagia. Approximately 3 weeks after completing induction chemoradiation, all patients underwent restaging evaluation. Using this pretreatment and posttreatment staging information, prognostic factors for freedom from recurrence and overall survival were identified. Results: The 36 months freedom from recurrence was 31% and overall survival 32%. Post-induction change in EGD tumor length and EUS TNM stage did not correlate with outcome. Resolution of symptomatic dysphagia, which occurred in 86%, was the strongest predictor for freedom from recurrence ( p &lt;0.001) and overall survival ( p &lt;0.001). Conclusions: EGD and EUS restaging of locoregional disease after induction concurrent chemoradiotherapy did not help to predict recurrence. The persistence symptomatic dysphagia, when coupled with advanced pretreatment stage, is ominous and predicts for incurable disease. Subsequent therapy should be considered palliative.

Is Neck Dissection Necessary After Induction Plus Concurrent Chemoradiotherapy in Complete Responder Head and Neck Cancer Patients with Pretherapy Advanced Nodal Disease?

The aim of the present study was to assess, in the setting of a single-institution prospective clinical trial, the necessity of planned neck dissection (PND) in physically and radiologically complete responders with pretherapy advanced nodal disease. Between January 2000 and July 2007 a total of 139 patients were enrolled to receive a regimen of platinum-based multidrug induction-concurrent chemoradiotherapy (IC/CCRT). A total of 75 of the enrolled patients with advanced nodal disease were included in this retrospective study. Between 8 and 12 weeks from the end of treatment, the response to IC/CCRT was evaluated by fiber-optic endoscopy and head and neck contrast-enhanced computed tomography or magnetic resonance imaging. The complete clinical response (cCR) rate was 68%. Among the 51 patients who achieved locoregional cCR at the end of CCRT, 8 underwent PND according to the study recommendation. Of the 43 patients with cCR who did not undergo PND, 2 patients (4.7%) experienced isolated regional recurrences with the 5-year regional control being 82%. Patients with cCR did not have a significantly lower regional control compared with patients with cCR who underwent ND (P=.962). Pathological evidence of residual disease was found in 81% of the patients with less than cCR who underwent ND. In physically and radiologically complete responders to IC/CCRT, a PND appears not justified. Conversely, PND should be performed in patients clinically suspected of having residual disease in the neck, as a significant proportion have viable tumor cell in post CCRT ND.

Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age (± 5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m(2), and a continuous infusion of 5-fluorouracil, 1,000 mg/m(2)/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

Predictive value of restaging after induction concurrent chemoradiotherapy (CCRT) for locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastroesophageal junction (GEJ).

4069 Background: CCRT has modest curative potential for LRA esophageal cancer and is commonly used preoperatively to improve surgical outcome. Although this approach can be curative, most patients ...

Is There a Standard of Care for the Radical Management of Non-small Cell Lung Cancer Involving the Apical Chest Wall (Pancoast Tumours)?

The term Pancoast tumour encompasses a wide range of tumours that invade the apical chest wall. Although less than 5% of non-small cell lung cancers are Pancoast tumours, they still account for most cases. They often pose a formidable challenge to the multidisciplinary lung cancer team due to their relative rarity, anatomical proximity to vital structures, differing stages of presentation, and their association with smoking-related illnesses. A lack of clinical trials makes comparisons between different treatment modalities very difficult and the management of Pancoast tumours has been largely based on the published retrospective experience of large single institutions. The bimodality approach of induction radiotherapy followed by surgical resection has been the accepted standard of care for the last 50 years, with reported 5-year survival rates of 30% in selected patients. However, two recent prospective multicentre phase II studies using a trimodality approach of induction concurrent chemoradiotherapy followed by surgical resection (followed by two further cycles of adjuvant chemotherapy in one of the studies), have reported 5-year survival rates of 44–56%. This has led to some authorities advocating the trimodality approach as the new standard of care for the management of Pancoast tumours. In this overview, the historical evolution of the management of Pancoast tumours and recent published studies on the trimodality approach are discussed. This is followed by a discussion of whether the trimodality approach should be seen as a new standard of care. Finally, other potential treatment options and the possibilities for future research are deliberated.

Induction concurrent chemoradiotherapy compared with induction radiotherapy for superior sulcus non‐small cell lung cancer: a retrospective study

To evaluate the efficacy of current chemoradiotherapy on improvement of survival in patients with superior sulcus non-small cell lung cancer (NSCLC). We retrospectively reviewed the data of 39 patients with superior sulcus NSCLC treated with induction therapy followed surgery. The patients were divided into two groups according to the induction approach: the induction radiotherapy (RT) group (1993-1999), and the induction chemoradiotherapy (CT/RT) group (since 1999). The rate of complete resection was 65 percent in the RT group (n = 17) compared with 91 percent in the CT/RT group (n = 22, P = 0.024). Complete pathological responses from induction therapy were 12 percent in the RT group and 45 percent in the CT/RT group (P = 0.032). Overall survival (OS) was significantly longer in patients who received CT/RT than that in those who received RT, with 2- and 5-year survival rates of 77.3 percent and 36.4 percent versus 41.2 percent and 11.8 percent, respectively (P = 0.007). CT/RT also associated with a markedly longer tumor-free survival (TFS), with a median TFS of 40 and 17 months, respectively (P = 0.007). Patients achieved complete resection or complete pathological response had a significantly better survival than those with incomplete resection or pathological partial responses and no change (P < 0.0005 and P = 0.001, respectively). Our results indicate that CT/RT followed by surgery can significantly improve OS and TFS, and may be considered as an optimal option in treatment of patients with superior sulcus NSCLC.