ABSTRACT
The definition of nodal and/or mucosal target volumes for radiation therapy for lymphadenopathies of unknown primary is controversial. Target volumes may include all nodal areas bilaterraly and be pan-mucosal or unilateral, selective, including the sole oropharyngeal mucosa. This review presents current recommendations in light of changes in the TNM classification, Human papillomavirus status and therapeutic advances. We conducted a systematic review of the literature with the following keywords: lymphadenopathy; head and neck; unknown primary and radiation therapy. There are no direct comparative studies between unilateral or bilateral nodal irradiation or pan-mucosal and selective mucosal irradiation. Contralateral lymph node failure rates range from 0 to 6% after unilateral nodal irradiation and 0 and 31% after bilateral irradiation. Occurrence of a mucosal primary varies between 0 and 19.2%. Initial clinical presentation and Human papillomavirus status are critical to define mucosal target volumes. Intensity-modulated radiotherapy is recommended (rather than three-dimensional irradiation) to avoid toxicities. Systemic treatments have similar indications as for identified primary head and neck cancers. Failures do not appear superior in case of unilateral nodal irradiation but comparative studies are warranted due to major biases hampering direct comparisons. Human papillomavirus status should be incorporated into the therapeutic strategy and practice-changing TNM staging changes will need to be evaluated.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Lymphatic Metastasis/radiotherapy , Neoplasms, Unknown Primary , Radiotherapy, Intensity-Modulated/methods , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/virology , Humans , Papillomavirus Infections/complications , Radiotherapy Dosage , Radiotherapy, Adjuvant , Radiotherapy, Image-GuidedABSTRACT
BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (nâ¯=â¯19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, nâ¯=â¯58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/secondary , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/secondary , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/mortality , Clinical Trials, Phase III as Topic , Disease Progression , Disease-Free Survival , France , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Multicenter Studies as Topic , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/mortality , Proportional Hazards Models , Retrospective Studies , Risk Factors , Testicular Neoplasms/diagnostic imaging , Testicular Neoplasms/mortality , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , United StatesABSTRACT
BACKGROUND: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. PATIENTS AND METHODS: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat® test. Biomarkers were correlated with efficacy outcomes. RESULTS: Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50-0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33-0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37-0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29-1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28-0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31-0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat 'Good' versus 'Poor' [2.7 versus 1.5 months; HR 0.71 (0.49-0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). CONCLUSIONS: Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. CLINICAL TRIAL REGISTRATION: NCT01345682.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/metabolism , Methotrexate/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/metabolism , Quinazolines/administration & dosage , Administration, Intravenous , Administration, Oral , Afatinib , Antimetabolites, Antineoplastic/administration & dosage , Biomarkers, Tumor/blood , Biopsy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/pathology , Disease-Free Survival , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/pathology , Humans , Neoplasm Metastasis , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Predictive Value of Tests , Squamous Cell Carcinoma of Head and NeckABSTRACT
BACKGROUND: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. PATIENTS AND METHODS: Patients received either first-line everolimus followed by second-line sunitinib at progression (n = 238) or first-line sunitinib followed by second-line everolimus (n = 233). Secondary end points were combined first- and second-line progression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of soluble biomarkers on OS were explored. RESULTS: At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months (95% CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9-1.6]. Median OS was 22.4 months (95% CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1; 95% CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimus and 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS with the association being largely independent of treatment sequences. CONCLUSIONS: Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression in patients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and there were no unexpected safety signals. CLINICAL TRIALS NUMBER: ClinicalTrials.gov identifier, NCT00903175.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Cross-Over Studies , Everolimus/administration & dosage , Female , Humans , Indoles/administration & dosage , Male , Middle Aged , Prognosis , Pyrroles/administration & dosage , Sunitinib , Survival Analysis , Young AdultABSTRACT
The long-term results of the EORTC 24954 trial comparing sequential versus alternating chemotherapy and radiotherapy (RT) for patients with locally advanced laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin-5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy and post-operative RT for the non-responders) and an alternating arm (AA = cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a total dose of 60 Gy). Median follow-up was 10.2 years. Ten-year survival with functional larynx (primary end-point) and overall survival were similar in both arms (18.7% and 33.6% in SA versus 18.3% and 31.6% in AA). Late toxicity was also similar; however, a trend for higher larynx preservation and better laryngeal function was observed in AA.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Hypopharyngeal Neoplasms/therapy , Laryngeal Neoplasms/therapy , Larynx , Organ Sparing Treatments/methods , Adult , Aged , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Disease Progression , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Humans , Hypopharyngeal Neoplasms/pathology , Laryngeal Neoplasms/pathology , Laryngectomy , Male , Middle Aged , Survival Analysis , Young AdultABSTRACT
BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND METHODS: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate. RESULTS: Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.
Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Neoplasms, Germ Cell and Embryonal/drug therapy , Adolescent , Adult , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Carboplatin/therapeutic use , Cisplatin/adverse effects , Cisplatin/therapeutic use , Disease-Free Survival , Epirubicin/adverse effects , Epirubicin/therapeutic use , Etoposide/adverse effects , Etoposide/therapeutic use , Female , Humans , Ifosfamide/adverse effects , Ifosfamide/therapeutic use , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/surgery , Paclitaxel/adverse effects , Paclitaxel/therapeutic use , Thiotepa/adverse effects , Thiotepa/therapeutic use , Treatment Failure , Young AdultSubject(s)
Antineoplastic Agents/adverse effects , Cancer Care Facilities/organization & administration , Emergency Medical Services/organization & administration , Referral and Consultation/organization & administration , Adult , Aged , Aged, 80 and over , Emergency Medical Services/statistics & numerical data , Female , France , Humans , Male , Medical Records/standards , Middle Aged , Prospective Studies , Referral and Consultation/statistics & numerical data , Skin/drug effects , Young AdultABSTRACT
BACKGROUND: The standard treatment of patients with metastatic germ-cell tumor (GCT) relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing three-drug regimen, which usually yields a complete response (CR) rate <50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study. PATIENTS AND METHODS: The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/day day 1-5, cisplatin 20 mg/m(2)/day day 1-5, and granulocyte colony-stimulating factor 263 µg/day day 7-15, repeated every 3 weeks for four cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous CR to first-line chemotherapy for metastatic disease. The primary end point was the CR rate and a two-stage Simon design was used. RESULTS: Thirty-seven patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3 and 4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression. CONCLUSION: In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate. CLINICAL TRIAL NUMBER: NCT00127049.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Germ Cell and Embryonal/drug therapy , Testicular Neoplasms/drug therapy , Adult , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Administration Schedule , Humans , Ifosfamide/administration & dosage , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/secondary , Prospective Studies , Salvage Therapy , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Treatment Outcome , Young Adult , GemcitabineABSTRACT
Head and neck cancers are the fifth among the most common cancers in France. Two thirds of cases occur at an advanced stage. For advanced disease, progression-free survival, despite undeniable progress, remains below 50% at three years. The last 20 years have been marked by the necessity to identify situations where less intense surgery and/or radiotherapy and/or chemotherapy is possible without jeopardizing the prognosis, and situations where a therapeutic intensification is necessary and results in a gain in survival while better preserving function with less toxicity. French cooperative groups gathering radiation oncologists (GORTEC), surgeons (GETTEC) and medical oncologists or physicians involved in the management of systemic treatments in head and neck cancers (GERCOR) are now belonging to the INCa-labelled Intergroup ORL to deal with the challenges of head and neck cancers.
Subject(s)
Otolaryngology/organization & administration , Otorhinolaryngologic Neoplasms/therapy , Radiation Oncology/organization & administration , Chemoradiotherapy/methods , Chemoradiotherapy/trends , Disease-Free Survival , France , Humans , Induction Chemotherapy/methods , Lasers, Gas/therapeutic use , Medical Oncology/organization & administration , Organ Sparing Treatments/methods , Otolaryngology/methods , Otolaryngology/trends , Otorhinolaryngologic Neoplasms/mortality , Otorhinolaryngologic Neoplasms/pathology , Otorhinolaryngologic Neoplasms/virology , Papillomavirus Infections/complications , Paranasal Sinus Neoplasms/surgery , Phototherapy/methods , Radiation Oncology/methods , Radiation Oncology/trends , Retreatment/methods , Robotics/methods , Sentinel Lymph Node BiopsyABSTRACT
BACKGROUND: Mammalian target of rapamycine (mTOR) inhibitors are being increasingly prescribed as antitumoural drugs, and associated adverse cutaneous effects are frequent but poorly described. The aim of this study was to describe such adverse effects and to assess the quality of life of patients experiencing them. PATIENTS AND METHODS: Over a period of 18 months, 18 patients treated with mTOR inhibitors for renal carcinoma were included and 77 dermatological examinations performed. Wherever a cutaneous adverse event was present, quality of life was evaluated using the Skindex 30 questionnaire. RESULTS: Fifteen of the 18 patients included presented adverse cutaneous events, consisting of buccal ulcers (61.1%), xerosis (55.5%), distal onycholysis (50%), acneiform eruption (38.8%), paronychia (22.2%) and pruritus (22.2%). Buccal ulcerations and perionyxis had an especially marked impact on quality of life, which was greatest in terms of physical score (19%), followed by emotional (9%) and functional (6%) scores. CONCLUSION: Cutaneous adverse effects of mTOR inhibitors are frequent and have a considerable impact on quality of life, particularly as regards physical scores. Dermatological examination appears useful to allow early management of cutaneous adverse effects and improve the quality of life of these patients.
Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/drug therapy , Drug Eruptions/etiology , Kidney Neoplasms/drug therapy , Sirolimus/analogs & derivatives , TOR Serine-Threonine Kinases/antagonists & inhibitors , Acneiform Eruptions/chemically induced , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Drug Eruptions/psychology , Emotions , Everolimus , Female , Humans , Ichthyosis/chemically induced , Male , Middle Aged , Onycholysis/chemically induced , Paronychia/chemically induced , Prospective Studies , Pruritus/chemically induced , Quality of Life , Severity of Illness Index , Sirolimus/adverse effects , Sirolimus/therapeutic use , Stomatitis, Aphthous/chemically inducedABSTRACT
BACKGROUND: Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN. PATIENTS AND METHODS: Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response. RESULTS: Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P=0.016), and an increase in the plasma level of tumor growth factor-alpha (P=0.006). CONCLUSION: Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Antibodies, Monoclonal , Biopsy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Gene Expression Profiling , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Immunoglobulins, Intravenous/adverse effects , Immunoglobulins, Intravenous/immunology , Receptor, IGF Type 1/antagonists & inhibitors , Receptor, IGF Type 1/immunology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND: Antiangiogenic agents may be associated with severe hand-foot reactions (HFR) requiring dose adjustment by oncologists. Many preventive and curative treatments are described in the literature but their efficacy has not been assessed in clinical trials. The aim of this study was to examine information given to patients about HFR and to evaluate compliance with prophylactic therapy for this complication. PATIENTS AND METHODS: Fifty-one patients receiving antiangiogenic therapy were followed up for a period of 19 months. At each visit, a dermatological examination was performed, compliance with topical treatment was assessed and advice was provided. At the end of the study, patients' perception of the information given was assessed by means of a questionnaire, completed either during consultations or by telephone. RESULTS: Although all patients were given information about HFR, 11 of 39 subjects claimed they had received no such information. There was no difference regarding compliance with topical treatment whether the information was provided by a dermatologist or an oncologist. Eleven patients consulted a podiatrist and nine patients used soft insoles. Twenty-two of 40 patients used topical treatments, with nine using such treatment from the outset. A statistically significant correlation was noted between compliance with preventive topical therapy and onset of HFR (P=0.028), and this finding merits confirmation in a larger-scale study. CONCLUSION: This study highlights the difficulties in implementing a programme to prevent HFR and suggests the value of providing multidisciplinary therapeutic education and of financing preventive and curative care.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Dermatologic Agents/therapeutic use , Emollients/therapeutic use , Hand-Foot Syndrome/drug therapy , Hand-Foot Syndrome/prevention & control , Indoles/adverse effects , Pyrroles/adverse effects , Administration, Cutaneous , Adult , Aged , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/drug therapy , Combined Modality Therapy , Dermatologic Agents/administration & dosage , Dermatology , Emollients/administration & dosage , Female , Hand-Foot Syndrome/etiology , Hand-Foot Syndrome/therapy , Humans , Indoles/administration & dosage , Indoles/therapeutic use , Kidney Neoplasms/complications , Kidney Neoplasms/drug therapy , Male , Medical Oncology , Medication Adherence , Middle Aged , Neoplasms/complications , Neoplasms/drug therapy , Orthotic Devices , Patient Education as Topic , Podiatry , Program Evaluation , Prospective Studies , Pyrroles/administration & dosage , Pyrroles/therapeutic use , Sunitinib , Surveys and QuestionnairesABSTRACT
AIMS: To understand management strategies and outcomes of patients diagnosed with a head and neck tumour and a synchronous second cancer developed at another anatomic site. MATERIALS AND METHODS: Retrospective analysis of all patients diagnosed with a head and neck carcinoma and a synchronous cancer and engaged in curative-intent treatments. To evaluate therapeutic strategies, each patient's treatment process was divided into sequential therapeutic modalities and corresponding targets (head and neck and/or synchronous tumour) were identified. Patient outcome was analysed with an intent-to-treat approach. RESULTS: Forty-three patients were entered into the study (mean age=57.4 years). Synchronous tumours concerned the lung (57.8%), oesophagus (31.1%) or other sites (11.1%). Treatments were complex, including one to four consecutive modalities, with a mean duration of 4.6 months. When both tumours were advanced, treatments were frequently initiated with dual-spectrum chemotherapy (66.7%). In other situations, a locoregional treatment was often (81.1%) proposed immediately. When both tumours were in early stages, this initial locoregional treatment could be extended to target both tumours together (30.0%). For patients whose tumours differed in severity, this locoregional treatment targeted only one tumour (85%); priority was given to the most advanced one (76.5%). Nine patients had definitive treatment interruption. Associated risk factors were a low body mass index (P=0.03) and advanced-stage tumours (P=0.01). Thirty-one patients died (72.1%) with a median time to death of 7.7 months. The median follow-up for survivors was 46.2 months. Three-year overall survival was 33.9%. Low body mass index (P=0.001), advanced-stage synchronous tumours (P=0.03) and oesophageal primaries (P=0.03) altered the overall survival. Three-year locoregional and metastatic progression-free survival was 40.8 and 62.5%, respectively. Low body mass index (P=0.01) and advanced-stage synchronous tumours (P=0.01) increased the risk of disease failure. CONCLUSIONS: Head and neck tumours diagnosed with a synchronous cancer are a complex challenge. Despite a severe prognosis, patients who are not underweight, presenting with lower-stage tumours (especially the synchronous tumour) and without oesophageal involvement could most benefit from aggressive treatments.
Subject(s)
Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/therapy , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/therapy , Combined Modality Therapy , Head and Neck Neoplasms/mortality , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/mortality , Radiotherapy , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: Endoscopic endonasal surgery let us observe that woodworkers' nasal adenocarcinomas originate in the olfactory cleft. Our aim was the identification of CT imaging features that corroborate the olfactory cleft as the site of origin for woodworkers' adenocarcinoma. MATERIALS AND METHODS: We designed a retrospective study to compare CT scans of 27 unilateral olfactory cleft adenocarcinomas with 30 cases of nasosinusal polyposis (NSP) and 33 healthy sinus controls. Enlargement of the olfactory cleft, lateralization of the ethmoidal turbinate wall, and contralateral bulging of the nasal septum were measured on coronal scans passing through crista galli and posterior half of both ocular globes. Comparisons have been performed by using analysis of variance and the Bonferroni procedure. RESULTS: The nasal septum was significantly bulging across the midline in adenocarcinoma (4.6 +/- 3 mm; range, -0.1-13.7 mm) compared with NSP (0.7 +/- 1 mm; range, -2.1-2.3 mm) or healthy sinus controls (0.5 +/- 1 mm; range, -1.2-2 mm) (P < .001). The olfactory cleft was significantly wider in adenocarcinoma (15.1 +/- 4.5 mm; range, 8.6-25.7 mm) than in NSP (3.6 +/- 0.4 mm; range, 2.8-4.6 mm) or healthy sinus controls (3.3 +/- 0.7 mm; range, 1.4-4.6 mm). The ethmoidal labyrinth width was significantly smaller on the pathologic side in adenocarcinoma (7.2 +/- 2.7 mm; range, 3.2-14.2 mm) than in the control groups (P < .001). Whereas the angle between the conchal lamina and vertical midline was close to zero degrees in NSP (0.03 +/- 2.25 degrees ; range, -5 degrees -3 degrees ) and healthy sinus controls (0.45 +/- 2.13 degrees , range, -5 degrees -5 degrees ), it reached 39.76 +/- 13.83 degrees (P < .001) in adenocarcinoma. CONCLUSIONS: Radiologists should suspect nasal adenocarcinoma on sinus CT scans showing a unilateral expanding opacity of the olfactory cavity.
Subject(s)
Adenocarcinoma/diagnostic imaging , Nasal Cavity/diagnostic imaging , Nose Neoplasms/diagnostic imaging , Occupational Diseases/diagnostic imaging , Tomography, X-Ray Computed/methods , Adolescent , Adult , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Chemotherapy, Adjuvant/methods , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/radiotherapy , Laryngectomy , Radiotherapy, Adjuvant/methods , Adult , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/physiopathology , Carcinoma, Squamous Cell/surgery , Chemotherapy, Adjuvant/adverse effects , Cisplatin/administration & dosage , Disease-Free Survival , Europe , Female , Fibrosis/etiology , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Laryngeal Edema/etiology , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/physiopathology , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Male , Middle Aged , Mucositis/etiology , Neoplasm Staging , Patient Selection , Radiotherapy Dosage , Radiotherapy, Adjuvant/adverse effects , Recovery of Function , Remission Induction , Research Design , Salvage Therapy/methods , Treatment Failure , Treatment OutcomeABSTRACT
OBJECTIVE: To report our experience in sentinel lymph node biopsy for lymphophilic conjunctival and eyelid tumours. METHODS AND RESULTS: Preliminary study (2005-2007) on 8 patients with conjunctival and or eyelid tumours (melanomas, epidermoid carcinoma, Merkel cell carcinoma). All patients underwent preoperative lymphoscintigraphy 18 FdG pet CT Surgery was performed with complete neck dissection. Sentinel nodes and other nodes harvested were processed separately for histopathologic study; the sentinel were confirmed as histologicaly positive for five patients. Additional positive nodes were found in two out of those five patients. No positive lymph node was found in patients with negative lymphoscintigraphy. After a follow up ranging from 12 to 43 months: two patients died, and 6 are free of disease. CONCLUSIONS: These results demonstrate a very hight level of invaded NO lymph node and confirm the interest of sentinel node technique for optimisation of the therapeutic strategy in lymphophilic conjunctival and eyelid tumours.