Randomized phase 3 noninferiority trial of radiotherapy and cisplatin vs radiotherapy and cetuximab after docetaxel-cisplatin-fluorouracil induction chemotherapy in patients with locally advanced unresectable head and neck cancer.

OBJECTIVES: Concurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT. MATERIALS AND METHODS: This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm). The primary endpoint was noninferiority of the experimental arm vs the standard arm in terms of overall survival (OS), based on a hazard ratio (HR) of < 1.3. Secondary endpoints included progression-free survival, overall response, safety, and quality of life (QOL). RESULTS: Between July 15, 2008, and July 5, 2013, 519 patients were recruited and started ICT; 407 patients received post-ICT treatment (cis+RT, n = 205; cet+RT, n = 202). At a median follow-up of 43.9 (cis+RT) and 41.1 (cet+RT) months, median OS was 63.6 and 42.9 months with cis+RT and cet+RT, respectively (HR [90% CI] = 1.106 [0.888-1.378], P =.4492). There were no differences in progression-free survival, overall response rates, or adverse event rates between groups. There was greater late neurotoxicity with cis+RT than cet+RT (P =.0058). Several QOL dimensions improved with cet+RT vs cis+RT (physical functioning, P =.0287; appetite loss, P =.0248; social contact, P =.0153). CONCLUSION: Noninferiority of cet+RT over cis+RT was not demonstrated.

Neck mass and tracheostomy in a young lady depicted by Piero di Cosimo.

Among surgical procedures currently in use, tracheostomy has a particularly long history. The first written description of the procedure is due to Brasavola, and dates from 1546. Piero di Cosimo (1462-1522) was an early Renaissance painter who painted a work traditionally known as Cephalus and Procris or The Death of Procris (1495-1500). In this painting, a vertical tracheostomy can be observed in a young woman lying on the ground. A giant mass can be seen in the lower left neck with superficial venous vessels, suggesting a thyroid malignancy. This appears to be the first detailed depiction of a malignant cervical mass and a possibly therapeutic tracheostomy. We discuss the clinical differential diagnosis and also make some comments from an art history perspective.

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results from the treatment of mucosal cancers.

AIM: Electrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours. PATIENT AND METHODS: Forty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life. RESULTS: Thirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment. CONCLUSION: Electrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer.

The Role of Audiometry prior to High-Dose Cisplatin in Patients with Head and Neck Cancer.

OBJECTIVES: To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients. METHODS: Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB. RESULTS: A total of 103 patients were included; the median age of the patients was 59 years (range 18-75). Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty-two participants (41%) did not commence high-dose cisplatin because of baseline audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40 (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss between initial and final audiometries showed a hearing loss at 4 and 8 kHz in both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a lower dose of cisplatin. The outcome was not significantly altered when cisplatin was replaced with carboplatin or cetuximab. CONCLUSIONS: Audiometric alterations are common in HNC with high-dose cisplatin, and switching to a less ototoxic regimen does not adversely affect outcome. Audiometric examination could help to prevent hearing loss in this population.

Could the Addition of Cetuximab to Conventional Radiation Therapy Improve Organ Preservation in Those Patients With Locally Advanced Larynx Cancer Who Respond to Induction Chemotherapy? An Organ Preservation Spanish Head and Neck Cancer Cooperative Group Phase 2 Study.

PURPOSE: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors. METHODS AND MATERIALS: This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT. Patients who did not respond to IC underwent total laryngectomy plus neck dissection and radiation therapy. RESULTS: A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [CI] 60%-79%); laryngectomy-free survival: 72% (95% CI 61%-81%); overall survival: 78% (95% CI: 63%-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT. CONCLUSIONS: According to this protocol, the SFL rate was clearly higher than the critical value, with acceptable levels of toxicity. The use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted.

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results of the treatment of skin cancer.

Electrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p < 0.05), as investigated by univariate analysis. Electrochemotherapy was well tolerated and led to a significant improvement of quality of life, estimated by the European Organisation for Research and Treatment of Cancer quality of life questionnaires. At 1-year follow-up, the percentages of overall and disease-free survival were 76% and 89%, respectively. Electrochemotherapy is an effective option for skin cancers of the HN area and can be considered a feasible alternative to standard treatments when such an alternative is appropriate. The precise role for electrochemotherapy in the treatment algorithm for non-melanoma skin cancer of the HN region requires data from future randomised controlled studies. (ISRCTN registry N. 30427).

Enrichment of Cells with Cancer Stem Cell-Like Markers in Relapses of Chemoresistant Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) present different responses to chemotherapy and radiotherapy. One explanation may be the differences in the individual rates of stem cell-like cells. METHODS: We included patients with HNSCC and tumor progression or relapse. Tumor samples were obtained before and after primary chemotherapy, and immunohistochemical analyses were performed for CD44, HLA class I (HLA-I), pancytokeratin, and phosphorylated epidermal growth factor receptor (p-EGFR). Differences in expression between the first and second specimens were assessed. RESULTS: Expression between the first and second specimens varied as follows: CD44 increased by 14.67% (95% confidence interval, CI: 6.94 to 22.40; p < 0.01); HLA-I decreased by 16.72% (95% CI: -23.87 to -9.47; p < 0.01); pancytokeratin decreased by 24.91% (95% CI: -32.8 to -17.7; p < 0.01), and p-EFGR expression decreased by 12.30% (95% CI: -20.61 to -3.98; p < 0.005). CONCLUSIONS: Among patients with HNSCC, there is an enrichment of cells with stem-like markers in relapsed tumors when compared with the primary tumor. This finding should be considered when developing treatment strategies.

A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. METHODS AND MATERIALS: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m(2) day 1; cisplatin, 75 mg/m(2) day 1; 5-fluorouracil [5-FU], 750 mg/m(2) day 1-5) and cetuximab, 250 mg/m(2) weekly (loading dose of 400 mg/m(2)). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. RESULTS: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). CONCLUSIONS: C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.

Outcome of patients treated with palliative weekly paclitaxel plus cetuximab in recurrent head and neck cancer after failure of platinum-based therapy.

Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled. Tumor response was evaluated through the response evaluation criteria in solid tumor criteria. The retrospective analysis focused on overall survival (OS) and progression-free survival (PFS). Between 2008 and 2011, 33 consecutive patients were treated. A response rate of 55% was observed, with median response duration of 5.0 months (95% CI 3.3-11.1). The median PFS was 4.0 months (95% CI 2.9-5.0) and the median OS time was 10.0 months (95% CI 7.9-12.0). Acne-like rash/Folliculitis and chronic anemia were the most common adverse events. A weekly schedule of Paclitaxel plus Cetuximab is a promising regimen for patients with advanced head and neck cancer after failure of platinum-based therapy. Good tolerance of this treatment suggests that would be used in fragile patients.

Prognosis in women with breast cancer and private extra insurance coverage.

BACKGROUND: Many women covered by the Spanish public health system also have an extra private insurance policy for gynecological examinations and routine annual mammography. We retrospectively analyzed the long-term survival rates in these patients when diagnosed with breast cancer. METHODS: We analyzed the survival and prognostic factors in patients diagnosed with breast cancer who were referred to a medical oncology unit for multidisciplinary treatment covered by private health insurance. RESULTS: Between 1994 and 2009, a total of 434 patients with breast tumor were analyzed: 33 in situ and 401 infiltrating. Among the infiltrating carcinomas, 38 were stage IV and 363 were stage I, II, or III. With a median follow-up of 62 months, the 5-year global survival rate was 91%: 97% for stage I, 94% for stage II, and 77% for stage III tumors. In the patients diagnosed by routine mammography, the 5-year survival rate was 96%, compared with 86% in those consulting their gynecologist after breast self-examination or for other symptoms (p=0.0159). Seventy-four percent were treated conservatively and experienced better survival than the 26% who underwent mastectomy (p=0.0024). Patients with disease with positive hormone receptors had a better survival rate (p=0.0264); hormone receptor status was the only independent prognostic factor in the Cox multivariate analysis. Postmenopausal patients who received adjuvant tamoxifen plus exemestane had a better prognosis than those who received tamoxifen alone (p=0.0203). CONCLUSIONS: Long-term survival rate was high in breast cancer patients with extra private insurance coverage. This is probably because disease was diagnosed at an early stage.

Metastatic adenoid cystic carcinoma of the salivary gland responding to cetuximab plus weekly paclitaxel after no response to weekly paclitaxel alone.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the salivary gland frequently develops lung metastases. In cases in which chemotherapy is indicated, resistance is a common phenomenon. New drugs, such as cetuximab, have been chosen to avoid this chemoresistance. METHODS AND RESULTS: A 54-year-old man was diagnosed with ACC of the right submandibular gland. He underwent a submandibular gland resection with adjuvant radiotherapy. Three years later, bilateral lung metastases were diagnosed and treated with various chemotherapy schedules, including paclitaxel without success. We obtained radiographic response, followed by disease stabilization for more than 1 year with the addition of cetuximab to paclitaxel administered at low weekly doses (metronomic schedule). CONCLUSION: This case demonstrates for the first time a reversion of primary resistance to chemotherapy in ACC that is currently considered chemoresistant by use of a combination of metronomic chemotherapy with new targeted agents such as cetuximab. Metronomic chemotherapy was also well tolerated and achieved long-term response.

Respuesta a quimioterapia metronómica en un carcinoma adenoide quístico metastásico de parótida / Response to metronomic chemotherapy in a metastatic adenoid cystic carcinoma of the Parotid Gland

Los tumores de glándulas salivares han sido considerados hasta hace pocos años quimiorresistentes. El tratamiento con quimioterapia está indicado en el contexto de enfermedad locorregional irresecable o enfermedad metastásica. La experiencia de quimioterapia en el carcinoma adenoide quístico de parótida se basa en estudios fase II; la mayoría con esquemas de quimioterapia en combinación y a dosis plenas, y sin evidencia de que aumenten la supervivencia. Se conoce como quimioterapia metronómica a la administración de agentes citotóxicos a bajas dosis y a intervalos cortos y regulares, sin interrupciones en el tratamiento. La mayoría de estudios demuestran una eficacia similar o incluso superior y una menor toxicidad que cuando se administra con la máxima dosis tolerada. Nuestro caso clínico muestra, por primera vez, la eficacia del paclitaxel y el cisplatino en monoterapia y a dosis metronómicas en el tratamiento del carcinoma adenoide quístico de parótida metastásico (AU)

Formerly, salivary gland cancer was considered to be chemoresistant. Chemotherapy is indicated when distant metastases or inoperable locorregional disease are observed, although the chemotherapy schedule is not well defined. Data on chemotherapy treatment for adenoid cystic carcinoma consist of phaseII trials. Most of these studies analyze therapies with a combination of agents at full dose, although there is no clear evidence that such treatment improves survival. The administration of cytotoxic agents with low doses at frequent, regular intervals with no drug-free interruptions is known as metronomic chemotherapy. Most head-to-head studies show similar or even superior therapeutic results with metronomic scheduling than with a maximum tolerated dose regime.Our case report shows for first time the clinical activity of low-dose paclitaxel and cisplatin chemotherapy given separately as a single agent in metastatic adenoid cystic carcinoma of the parotid (AU)

[Response to metronomic chemotherapy in a metastatic adenoid cystic carcinoma of the parotid gland]. / Respuesta a quimioterapia metronómica en un carcinoma adenoide quístico metastásico de parótida.

Formerly, salivary gland cancer was considered to be chemoresistant. Chemotherapy is indicated when distant metastases or inoperable locorregional disease are observed, although the chemotherapy schedule is not well defined. Data on chemotherapy treatment for adenoid cystic carcinoma consist of phase II trials. Most of these studies analyze therapies with a combination of agents at full dose, although there is no clear evidence that such treatment improves survival. The administration of cytotoxic agents with low doses at frequent, regular intervals with no drug-free interruptions is known as metronomic chemotherapy. Most head-to-head studies show similar or even superior therapeutic results with metronomic scheduling than with a maximum tolerated dose regime. Our case report shows for first time the clinical activity of low-dose paclitaxel and cisplatin chemotherapy given separately as a single agent in metastatic adenoid cystic carcinoma of the parotid.

[The role of chemotherapy in advanced oral cavity cancer]. / El papel de la quimioterapia en el cáncer de la cavidad oral avanzado.

OBJECTIVE: To evaluate the role of chemotherapy in advanced cancer of the oral cavity by assessing its influence on the survival of patients receiving palliative care and its ability to improve the expectations of curative surgery. PATIENTS AND METHOD: Ninety-nine consecutive patients were analyzed to assess their course, the prognostic factors for tumour progression, and overall survival after treatment with two different chemotherapy regimes: cisplatin plus bleomycin (n=45) or cisplatin plus 5-fluorouracil (n=52). For the analysis, patients were split into groups depending on the treatment intention: palliative (n=41) or neo-adjuvant (n=56). RESULTS: The response rate was 56.7%. The response was greater in the neo-adjuvant group (73.2%) than among the palliative patients (36.6%) (P<0.001); greater with the bleomycin regime (73.3%) than with 5-fluorouracil (44.2%) (P=0.003); and greater in patients with stage III (77.8%) than stage IV (50%) (P=0.021). Survival was higher among patients receiving bleomycin than in those on 5-fluorouracil (P=0.019) and among those with stage III than stage IV (P=0.013). In the palliative treatment group, the response was associated with greater survival (P<0.001). In the neo-adjuvant group, 30 patients (53.6%) underwent surgery, with complete resection in 26 of them (86.7%). Sixteen cases (61.5%) presented recurrence. Chemotherapy response was not associated with operability. Survival was higher in the group with complete tumour resection (P<0.041). CONCLUSIONS: The response to chemotherapy in oral cavity tumours was greater in patients with stage III and in those receiving bleomycin. Chemotherapy may improve survival in palliative cases. In neo-adjuvant cases, no great influence was seen in the conversion of doubtful cases into candidates for surgery.

El papel de la quimioterapia en el cáncer de la cavidad oral avanzado / The role of chemotherapy in advanced oral cavity cancer

Objetivo: Valorar el papel de la quimioterapia en el cáncer avanzado de cavidad oral valorando su influencia en la supervivencia de los pacientes considerados como paliativos y su capacidad para mejorar las expectativas de cirugía curativa. Pacientes y método: Noventa y nueve pacientes consecutivos fueron analizados para valorar su evolución, los factores pronósticos de la progresión del tumor y la supervivencia global después del tratamiento con dos regímenes diferentes de quimioterapia: cisplatino más bleomicina (BLM) (n ¼ 45) o más 5-fluorouracilo (5-FU) (n ¼ 52). El análisis se realizó dividiendo los pacientes de acuerdo con la finalidad del tratamiento: paliativo (n ¼ 41) o neoadyuvante (n ¼ 56). Resultados: La tasa de respuesta fue del 56,7%. La respuesta fue mayor en el grupo neoadyuvante (73,2%) que en el grupo paliativo (36,6%) (po 0,001), mayor con el régimen de BLM (73,3%) que con 5-FU (44,2%) (p ¼ 0,003) y mayor en pacientes con estadio III (77,8%) que IV (50%) (p ¼ 0,021). La supervivencia fue mayor en pacientes que recibieron BLM que en los que recibieron 5-FU (p ¼ 0,019) y en el estadio III que en el IV (p ¼ 0,013). En el grupo paliativo, la respuesta se asoció a una mayor supervivencia (po0,001). En el grupo neoadyuvante, 30 pacientes (53,6%) fueron intervenidos y la resección fue completa en 26 de ellos (86,7%). Dieciséis casos (61,5%) presentaron una recidiva. La respuesta a la quimioterapia no se asoció a la operabilidad. La supervivencia fue mayor en el grupo con una resección completa del tumor (p ¼ 0,041). Conclusiones: La respuesta a la quimioterapia en los tumores de cavidad oral fue mayor en los pacientes con estadio III y en los que recibieron BLM. La quimioterapia puede mejorar la supervivencia en casos paliativos. En los casos neoadyuvantes no se demostró una gran influencia para convertir casos dudosos de cirugía en tributarios para cirugía (AU)

Objective. To evaluate the role of chemotherapy in advanced cancer of the oral cavity by assessing its influence on the survival of patients receiving palliative care and its ability to improve the expectations of curative surgery. Patients and method. Ninety-nine consecutive patients were analyzed to assess their course, the prognostic factors for tumour progression, and overall survival after treatment with two different chemotherapy regimes: cisplatin plus bleomycin (n=45) or cisplatin plus 5-fluorouracil (n=52). For the analysis, patients were split into groups depending on the treatment intention: palliative (n=41) or neo-adjuvant (n=56). Results. The response rate was 56.7%. The response was greater in the neo-adjuvant group (73.2%) than among the palliative patients (36.6%) (P <0 001 greater with the bleomycin regime 73 3 than 5-fluorouracil 44 2 P=0.003); and greater in patients with stage III (77.8%) than stage IV (50%) ( P=0.021). Survival was higher among patients receiving bleomycin than in those on 5-fluorouracil (P=0.019) and among those with stage III than stage IV (P=0.013). In the palliative treatment group, the response was associated with greater survival (P <0 001). In the neo-adjuvant group, 30 patients (53.6%) underwent surgery, with complete resection in 26 of them (86.7%). Sixteen cases (61.5%) presented recurrence. Chemotherapy response was not associated with operability. Survival was higher in the group with complete tumour resection (P <0 041). Conclusions. The response to chemotherapy in oral cavity tumours was greater in patients with stage III and in those receiving bleomycin. Chemotherapy may improve survival in palliative cases. In neo-adjuvant cases, no great influence was seen in the conversion of doubtful cases into candidates for surgery (AU)

Gene single nucleotide polymorphism accumulation improves survival in advanced head and neck cancer patients treated with weekly paclitaxel.

OBJECTIVES/HYPOTHESIS: Single nucleotide polymorphisms (SNPs) of certain genes involved in drug metabolism correlate with survival. METHODS: We evaluated the presence of SNPs in six genes (CYP2C8, GSTT1, GSTP1, MDR1-57, MDR1-62, and ERCC1) and the response rate (RR), time to progression (TTP), and overall survival (OS) of advanced head and neck cancer patients treated with weekly paclitaxel. RESULTS: SNPs in CYP2C8, MDR1-57, and MDR1-62 genes were more frequent than wild-type genes in our patients. RR was 45% (21/47), and median TTP in responders was 5.1 months. OS for all patients was 5.6 months. Response was higher in SNPs of MDR1-62, MDR1-57, or in two or more accumulated genes than in those with wild-type genes. OS was significantly longer in patients with two or more accumulated SNPs (P = .039). CONCLUSIONS: Response rate and OS were significantly higher in patients with two or more accumulated SNPs.

Dihydropyrimidine dehydrogenases and cytidine-deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: Single nucleotide polymorphisms of dihydropyrimidine dehydrogenases gene (DPYD) induces dihydropyrimidine dehydrogenase enzyme (DPD) deficiency resulting in increased activity of 5-fluorouracil derivatives. Cytidine-deaminase gene (CDA) polymorphisms have been involved in prognosis in experimental tumours. METHODS: Analysis of 50 consecutive resected gastric cancer patients who received adjuvant chemotherapy with Tegafur for polymorphisms of genes DPYD1 (A/G; Ile543Val), DPYD2 (C/T; Arg29Cys) and CDA (A/C; Lys27Gin). The status of alleles (wild-type or at least one polymorphism) was correlated with outcome and toxicity. RESULTS: Polymorphisms frequencies wild-type/non-wild-type were 36/14 in DPYD1 (A/G; Ile543Val); 26/24 in DPYD2 (C/T; Arg29Cys); and 17/23 in CDA (A/C; Lys27Gin) or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow-up (SD = 26.3), 18 patients died of tumour relapse. Better survival was observed in DPYD1 patients only, for non-wild-type over wild-type (P = 0.0214); and in patients with one or more heterozygous polymorphisms in any of the three genes tested (P = 0.0017). In 10 pts (20%) total dose was reduced by toxicity, only 3 of them were homozygous. CONCLUSIONS: Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.

Old masters as clinical photographers: multifocal breast cancer diagnosed 400 years ago.

It is common belief among physicians the idea that breast cancer was not diagnosed centuries ago. Nevertheless, there are reports suggesting that old masters and even common people knew this dramatic disease. In the 16th and 17th centuries, famous artists painted things exactly as they saw them. This allows the detection of breast tumours, as have been previously published. We have discovered a new case of breast cancer in an engraving after Titian's painting. The woman in the painting shows two tumour masses in her right breast, with skin and nipple retraction to the homo lateral axila, suggesting a multifocal breast cancer. Other diagnostic options, such as breast tuberculosis or Mondor's disease, have to be established. The findings suggest that this is the first imaging report of a multifocal breast cancer. Old masters acted, in fact, as clinical photographers.