Advanced-stage Squamous Cell Carcinoma Research Articles

Organ preservation for patients treated with induction chemotherapy (IC) followed by radiation therapy (RT) or chemoradiation (CRT) for advanced stage squamous cell carcinoma of the larynx (SCCL)

5600 Background: We reviewed the charts of patients with laryngeal cancer treated with IC and definitive RT or CRT to determine the rates of overall organ preservation and function. Methods: Between September 1995 and December 2001, 29 patients with stage III (45%) and IV (55%) SCCL, were treated with IC and definitive RT or CRT on one of seven consecutive trials. The median age at diagnosis was 54 years (range 38–74). 55% had clinically node-positive disease. 55% and 45% had T3 and T4 tumors, respectively. All received 3 cycles of IC with a platinum-based regimen. QD RT was given to 48%, BID RT to 45%, and concomitant boost (CB) RT to 7%. CRT was given with carboplatin (28%) or docetaxel (28%). Those treated with BID RT did not receive CRT. Results: Median follow-up is 52 months (range 17–85). Overall survival is 66%. Relapse occurred in12 (41%) patients, and 6 underwent salvage laryngectomy (5 Stage III, 1 Stage IV). Of the entire cohort, 59% (17/29) are alive at last follow-up with an anatomically inta...

Results from the treatment of advanced stage squamous cell carcinoma of the nasal planum in cats, using a combination of intralesional carboplatin and superficial radiotherapy: a pilot study

Six cats with an advanced stage squamous cell carcinoma (SCC) of the nasal planum were treated with a combination of superficial radiotherapy and intralesional carboplatin therapy. This multimodality protocol was well tolerated by the majority of cats and resulted in complete responses in all cats (100%). Median follow-up for all cats is 268 days, and the median time-to-recurrence, time-to-progression and overall survival have not yet been reached. Our study, although limited in number of animals and with a relatively short median follow-up compared to other studies for this disease, suggests that a combination of radiotherapy and intralesional carboplatin is a useful treatment option for an advanced stage SCC of the nasal planum in cats and warrants further application of the multimodality approach presented here.

Treatment of recurrent and advanced stage squamous cell carcinoma of the head and neck

Despite advances in our ability to safely treat patients with recurrent cancer of the upper aerodigestive tract, outcomes for retreatment are generally poor and the first chance to cure these patients remains the best chance. Thorough knowledge of the outlook and options for patients with recurrent disease is also of significance in choosing therapy for patients with newly diagnosed disease. This is especially true for newly diagnosed patients making the choice between surgery and nonsurgical (“organ-sparing”) options, who need to know the outlook for salvage surgery, should they recur after radiation with or without concomitant chemotherapy. Salvage surgery is generally the best option for previously irradiated patients who are faced with resectable, recurrent disease. Unfortunately, the results of surgical salvage are generally poor for patients with advanced stage recurrence and for those who recur after treatment of advanced disease. The site of initial and recurrent disease is important. Surgical salvage is most effective for patients with recurrent laryngeal cancer, least effective for recurrent cancer of the pharynx, and is intermediate for recurrence in the oral cavity. Patients choosing nonsurgical treatment for newly diagnosed cancer of the pharynx cannot rely on salvage surgery in the event of recurrence. Reirraditation for patients who have failed initial treatment that included radiation therapy has been used at a number of institutions with some success. Experience using reirradiation with or without concomitant chemotherapy continues to evolve. Palliative chemotherapy is an option for most patients, but response rates are generally poor and of short duration, after failure of initial treatment that includes radiation therapy. The best approach for many patients and families who face advanced recurrent disease is honest but compassionate communication and supportive care with the help of a hospice organization.

Impact of retropharyngeal lymph node metastasis in head and neck squamous cell carcinoma.

The impact of metastasis to the retropharyngeal lymph node (RPLN) group is poorly understood because of the difficult access of the retropharyngeal space. Previous studies concluding to the negative impact of RPLN metastasis rely heavily on radiographic assessment, which introduces the possibility of diagnostic error. To better define the prognostic significance of metastatic retropharyngeal adenopathy in patients with non-nasopharyngeal squamous cell carcinoma of the head and neck. A retrospective cohort study of patients with non-nasopharyngeal squamous cell carcinoma of the head and neck who underwent resection of the RPLN group and were followed up for an average of 24 months. Tertiary care academic medical center. The 51 patients included in the study had been treated for advanced-stage squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and/or supraglottic larynx via a surgical approach to the primary tumor that afforded access to the RPLN group. All patients underwent dissection and pathologic interpretation of the RPLNs, most patients received postoperative radiotherapy, and 43 patients met survival analysis criteria. Local and regional recurrence rates, the development of distant metastasis, and disease-free and overall survival. Metastasis to the RPLN group was confirmed pathologically in 14 (27.5%) patients. There was no statistically significant difference between patients with and without RPLN metastasis in rates of local recurrence (24.8% vs 28.4%), regional recurrence (17.5% vs 19.6%), distant metastasis (17.0% vs 11.2%), disease-free survival (40.5% vs 30.5%), and overall survival (40.6% vs 38.5%). Metastasis to the RPLN group does not impact disease control or survival in patients with advanced non-nasopharyngeal squamous cell carcinoma of the head and neck treated with multimodality therapy.

Concurrent Weekly Paclitaxel, Radiotherapy and SQ Amifostine in Patients with Advanced Stage Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Objectives: 1) To determine feasibility and outcome of treating patients with advanced SCCHN using concurrent low- dose weekly Paclitaxel and radiation therapy; 2) To study the role of SQ Amifostine as a radiation protectant. Methods: Previously untreated patients with stage III and IV SCCHN were eligible. From Oct 1998 to June 2001, 38 patients were treated with 30 mg/m2 of Paclitaxel given weekly over 1 hour with concurrent once a day radiation (2Gy/day;total dose 70 Gy), with no planned breaks. There were 32 patients with stage IV disease. Primary tumor sites included oropharynx (23), larynx (7), hypopharynx (7) and parotid (1). SQ Amifostine was added to the protocol in early 2001; 7 patients have received this drug. Results: At the end of the planned treatment the Response Rate (CR + PR) was 100%; 25 pts(66%) achieved a CR at both neck and primary. Nine pts(24%) had residual lymphadenopathy, underwent neck dissections and are now NED. The ultimate locoregional control rate is 89%; 3 pts died of progressive disease, one died of intercurrent disease. With a median followup of 24 months, 34 pts(89%) are alive and NED. Organ preservation was achieved in 100%. Thirty(79%) finished the radiotherapy dose as planned, 64% received all 7 cycles of Paclitaxel. Grade 3 mucositis was observed in 36% pts and these were the only pts who required a treatment break. Eight pts(21%) required a PEG tube for feeding; median weight loss was 10%. There were no complications durng the administration of SQ Amifostine. Conclusion: This treatment is feasible and highly active in the treatment of locally advanced SCCHN. Although the followup for patients treated with Amifostine is short, it appears that the addition of this drug in our protocol resulted in reduced early and late toxicity.

Neoadjuvant and Concomitant Chemotherapy and Radiotherapy for Advanced Head and Neck Carcinoma

Otero-Garcia, Jose E. MD; Ahmad, Faheem MD; Ensley, John F. MD; Jacobs, John R. MD; Yoo, George H. MD; Kim, Harold E. MD Author Information

Changing patterns of failure of head and neck cancer.

With the increased use of neoadjuvant therapy for advanced stage squamous cell carcinoma of the head and neck, we have observed an apparent change in the pattern of failure from predominantly locoregional sites to distant metastases. We reviewed the patterns of failure in cancers of the oral cavity, oropharynx, and larynx at our institution during the last decade. To determine whether there has been a significant change in the patterns of recurrence from the historical locoregional failure to distant sites, and whether this change is associated with the increased use of multimodality therapy. We reviewed cancer registry data on patients with squamous cell carcinoma of the head and neck diagnosed between January 1, 1988, and December 31, 1999. Sites included the oral cavity and oropharynx (including the tongue, floor of mouth, retromolar trigone, gingiva, tonsil, and lip) and larynx. Among 432 patients with squamous cell carcinoma of the head and neck, 280 (65%) had oral cavity and oropharyngeal cancers, and 152 (35%) had laryngeal cancers. Overall, 19% developed locoregional recurrence, and 8% developed distant failure. Although locoregional failure for oral cavity and oropharyngeal squamous cell carcinoma decreased from 26% to 16% from 1988-1993 to 1994-1999, distant failure increased significantly from 3% to 8%. During these periods, multimodality therapy was used in 62% of oral cavity and oropharyngeal cancers, and this rate remained essentially unchanged. For laryngeal cancer, locoregional and distant failure remained stable at 18% and 9%, respectively. In these laryngeal cancers, the use of multimodality therapy decreased from 60% to 46%, but this difference was not statistically significant (P =.43). Although locoregional control in oral cavity and oropharyngeal cancers has improved significantly with the use of multimodality therapy, the incidence of distant failure has doubled. In laryngeal squamous cell carcinoma, the patterns of failure have not changed significantly.

Predictive factors for diagnosis of advanced-stage squamous cell carcinoma of the head and neck.

To identify the predictive factors (with emphasis on diagnostic delay) associated with the diagnosis of an advanced-clinical stage head and neck cancer. Cross-sectional study of patients with head and neck cancer originally recruited for a case-control study. Three referral oncological centers in metropolitan areas in southern Brazil: São Paulo, Curitiba, and Goiânia. The study population comprised 679 patients recently diagnosed as having a previously untreated head and neck squamous cell carcinoma. Diagnosis of advanced disease (clinical stage III-IV) head and neck cancer. Patients with laryngeal and hypopharyngeal cancers were more likely to be diagnosed as having advanced disease than those with lip, oral, and oropharyngeal cancers (88.0% vs 74.6%) (P<.001). Patient delay was inversely associated with clinical stage at diagnosis in patients with the same cancers, while professional delay was directly associated with a higher risk of advanced clinical stage at diagnosis (P =.001 and P =.006, respectively). In the analysis of laryngeal and hypopharyngeal cancer, both patient and professional delays were associated with advanced disease, with patient delay being a stronger predictive factor than professional delay. Clinical stage at diagnosis was associated with sociodemographic characteristics, patient delay, and professional delay. Our results indicate that continued educational programs for the population and health care professionals regarding the identification of early symptoms of head and neck cancers are warranted.

Presentation, treatment, and outcome of oral cavity cancer: A national cancer data base report

Oral cancer has been identified as a significant public health threat. Systematic evaluation of the impact of this disease on the US population is of great importance to health care providers and policy makers. This study used the National Cancer Data Base (NCDB) to evaluate associations between demographic and disease characteristics, treatment, and survival for patients with oral cavity cancer in the United States. Of patients diagnosed between 1985 and 1996, 58,976 were extracted from the NCDB. ANOVAs were performed on selected cross-tabulations, and relative survival was used to calculate outcome. Median age of patients was 64.0 years. Men made up 60.2% of patients. Pathologic diagnosis was squamous cell carcinoma (SCC) in 86.3% of cases. Younger patients had a much higher frequency of non-SCC, and this was related to survival in these patients. African-Americans (independent of income), lower income patients, and patients with higher grade disease were seen more frequently with advanced-stage SCC. Five-year relative survival for SCC cases was lower for older patients, men, and African-Americans. This study addressed many issues related to oral cancer that have been previously discussed in the literature. The demographic, site, stage, histologic, and survival data available for this large number of cases in the NCDB allowed an accurate characterization of the contemporary status of oral cancer in the United States.

RCAS1 antigen is highly expressed in extramammary Paget's disease and in advanced stage squamous cell carcinoma of the skin

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is a type II membrane protein expressed on cervical carcinoma cells, induces apoptosis in RCAS1 receptor expressing cells. RCAS1 is thus presumed to protect tumor cells from immune surveillance by infiltrating RCAS1 receptor-positive immunocytes (Sonoda et al. Int J Oncol 1995; 6: 1899–1904; Nakashima et al. Nature Med 1999; 5: 938–942). We performed immunohistochemical analysis of RCAS1 expression in various skin tumors. RCAS1 was not detected in normal human epidermis. One of 21 seborrheic keratosis (4.8%), one of 12 actinic keratosis (8.3%), two of 16 keratoacanthomas (12.5%), and two of 14 basal cell carcinomas (14.2%) expressed RCAS1. RCAS1 was not detected in Bowen's disease (0/17). RCAS1 was positive in 45 of 61 (73.8%) squamous cell carcinomas. Interestingly, the expression of RCAS1 was mostly correlated with clinical stages of squamous cell carcinoma. It was found that 46.1% of stage I, 61.1% of stage II, 85.7% of stage III, and 83.3% of stage IV squamous cell carcinomas were RCAS1-positive. In addition, RCAS1 was found to be highly expressed in extramammary Paget's disease. Fifty nine of 63 extramammary Paget's disease samples (93.7%) were positive for RCAS1. Fifty eight (92%) showed co-expression of RCAS1 and carcinoembryonic antigen (CEA). While two of 24 cases of melanoma (8.3%) expressed RCAS1 antigen, none of 20 cases of nevus pigmentosus showed positive staining. These results indicate that RCAS1 is a highly sensitive marker for extramammary Paget's disease. RCAS1 is also expressed in various skin tumors including squamous cell carcinoma, where positive correlation with clinical staging was documented.

Advanced stage squamous cell carcinoma arising from mature cystic teratoma of the ovary

Advanced stage squamous cell carcinoma arising from mature cystic teratoma of the ovary

Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression.

We have previously reported that loss of p53 tumor suppressor protein results in centrosome hyperamplification, which leads to aberrant mitosis and chromosome instability. Since p53 is either deleted or mutated in human cancers at a high frequency, we investigated whether human cancers showed centrosome hyperamplification. Screening of advanced stage breast ductal carcinomas and squamous cell carcinomas of the head and neck (SCCHN) revealed that centrosome hyperamplification is frequent in both tumor types. Moreover, through the analyses of p53 in SCCHN samples by direct sequencing and by loss-of-heterozygosity test, we found that p53 mutations correlated with occurrence of centrosome hyperamplification. However, in some cases, we observed centrosome hyperamplification in tumors that retained wild-type p53. These tumors contained high levels of Mdm2. Since Mdm2 can inactivate p53 through physical association, we investigated whether Mdm2 overexpression induced centrosome hyperamplification. We found that Mdm2 overexpression, like loss of p53, induced centrosome hyperamplification and chromosome instability in cultured cells.

2183 Patterns of treatment by race and income for advanced-stage laryngeal squamous cell carcinoma

2183 Patterns of treatment by race and income for advanced-stage laryngeal squamous cell carcinoma

CURRENT OPTIONS IN MANAGEMENT OF HEAD AND NECK CANCER PATIENTS

Head and neck cancer, particularly squamous cell carcinoma (SCC) of the upper aerodigestive tract, poses difficult diagnostic and therapeutic challenges to the clinician. A methodical approach, including complete visualization of mucosal surfaces, appropriate imaging, and tissue diagnosis whenever possible, gives patients the best opportunity for early intervention. A treatment program of surgery, radiation, or chemotherapy is best developed by a devoted head and neck oncologic team, involving surgeons, radiation and medical oncologists, and rehabilitative specialists with significant experience in the care of head and neck oncologic patients. Despite new advancements in the treatment of patients with advanced stage SCC of the head and neck, little progress has been made in overall survival. Several new avenues of investigation are currently being explored, one of which may ultimately provide the answer for this devastating disease.

Photodynamic therapy response in cats with cutaneous squamous cell carcinoma as a function of fluence.

The response of advanced stage cutaneous squamous cell carcinomas (SCC) following treatment with photodynamic therapy (PDT) has been poor. It was the aim of this pilot study to determine whether an increase in the delivered fluence (i.e. energy density) would improve the duration of tumour remission in cats with advanced-stage SCC. Tumours were treated with aluminium phthalocyanine tetrasulphonate (AlPcS4 ) PDT at a fluence of either 100 J cm-2 or 200 J cm-2 and tumour response was evaluated at regular intervals. Those feline tumours treated with a fluence of 100 J cm-2 (n= 8) had a significantly shorter median remission duration (69 days; range 0-619 days) than those feline tumours treated with 200 J cm-2 (n= 6; 522 days; range 151-1057 days). It is our conclusion that a fluence of 200 J cm-2 is well tolerated and more effective when treating cats with advanced stage cutaneous SCC.

Different KGF Expression in Squamous Cell Carcinomas of the Head and Neck and in Normal Mucosa

Fibroblast growth factors (FGFs) are major factors mediating epithelial-mesenchymal interactions in the epidermis and mucosa. In this study the expression of the FGFs keratinocyte growth factor (KGF), acidic FGF (aFGF) and basic FGF (bFGF) was examined in tumour tissue specimens from 14 patients with advanced-stage squamous cell carcinoma of the head and neck (SCCHN) and 3 SCC cell lines by reverse-transcribed polymerase chain reaction (RT-PCR) and immunohistochemistry. None of the SCC cell lines was positive for KGF mRNA, whereas all cell lines were highly positive for aFGF and bFGF. In SCCHN tissue samples the level of KGF mRNA expression was significantly lower than in normal mucosa. Tumour stroma and the submucosal areas of normal mucosa stained intensely with anti-KGF antibody in immunohistochemical slides, whereas tumour cell nests were negative. Exposure of SCC cells to KGF thus differs from normal mucosa both quantitatively and regarding spatial distribution. This fact and the overexpression of aFGF and bFGF by tumour cells potentially promote tumour growth, invasion and metastasis. Since these growth factors and their receptors are well characterized, these observations could lead to new therapeutic strategies in SCCHN, for instance by blocking their receptors or antisense targeting.

Myocutaneous flaps in patients with head and neck cancer retain their immunological capacities in an activated functional state.

Free/pedicled myocutaneous flaps used as functional replacement after radical dissection of advanced stage squamous cell carcinomas of the oral cavity/oropharynx were examined by immunohistochemistry (APAAP-technique). Biopsies from eight patients were taken at the time of surgery and at 3 and 5 months post-operatively. Fifteen monoclonal antibodies were used to detect surface antigens as markers of phenotypic changes of immune competent cells. In post-operative biopsies all antigens investigated increased significantly. Significantly higher numbers of CD45RO+ (P < 0.01) and CD45RA+ (P < 0.001) leukocytes were detectable. The majority of these leukocytes were TcR alpha/beta +/CD3+ T-cells, which increased in the CD4 (P < 0.05) and the CD8 (P < 0.001) subset. In addition, B-cells (P < 0.05), granulocytes (P < 0.05), NK cells (CD16+ lymphocytic cells; P < 0.05) and mature macrophages (25F9+cells; P < 0.01) were increased. Intra- and subepidermally a significantly (P < 0.01) higher number of dendritic-/Langerhans cells (CD1a+) was detectable. In post-operative biopsies, the activation-associated antigens ICAM-1, VCAM and HLA-DR were expressed on significantly more mononuclear-/endothelial cells and on keratinocytes. Our findings indicate that the myocutaneous flaps still contained cells with immunological capacities.

Dual sequential non-cross-resistant chemotherapy for advanced stage squamous cell carcinoma of the cervix

Forty-three patients with recurrent and metastatic squamous cell carcinoma of the cervix received a program of sequential combination chemotherapy incorporating induction with cisplatin, vinblastine, and bleomycin (PVB) and subsequent consolidation with 5-fluorouracil, doxorubicin, cyclophosphamide, and vincristine (FACV). The overall response rate was 62% and 10 patients (23%) achieved complete remission. Response status was improved in 11 patients at the completion of FACV after initial PVB therapy, including 9 complete remissions. The median survival for all patients in the study was 38 weeks and 50 weeks for the responding patients. Myelosuppression was the principal toxicity encountered and 10 episodes of neutropenic sepsis occurred, including one septic death. However, the only cumulative toxicity was peripheral neuropathy, although this was only moderate to severe in 2 patients. These results are encouraging, but will require confirmation in randomized comparison to cisplatin, presently accepted as standard single-agent therapy

Concomitant cisplatin and hyperfractionated external beam irradiation for advanced malignancy of the head and neck

The combination of cisplatin and hyperfractionated external beam irradiation (HEBI), followed by salvage surgery when indicated, was evaluated in patients with advanced stage squamous cell carcinoma of the head and neck. Thirty patients with stage III (n = 5) or IV (n = 25) disease received intravenous cisplatin 100 mg/m 2 by 6-hour continuous infusion on days 1, 21, and 42 of HEBI. Radiation fractions of 110 cGy were given twice daily, separated by 4 to 6 hours, beginning within 12 hours after cisplatin delivery. Doses to the primary site ranged from 60 to 76.35 Gy (median: 72.3 Gy), with 60 to 74 Gy to nodal sites. Follow-up ranged from 4 to 28 months (median: 19 months). Clinical complete response of the primary site was seen in 27 of 29 patients (93%), and complete clinical clearance of adenopathy in 20 of 26 (76%). A second biopsy 6 to 8 weeks after completion of treatment showed residual disease in both the primary and nodal sites in three patients, and in only the primary site in one patient. Four patients with persistent adenopathy had pathologic confirmation at surgery. Four patients had recurrence after negative biopsy results 6 to 9 months after treatment biopsy. At present, with median follow-up of 19 months, eight patients (26%) have died secondary to uncontrolled primary or nodal disease. Two patients have died of nonrelated causes. Overall, 10 of 30 patients (66%) remain alive with no evidence of disease. Mucositis and weight loss were the most common side effects of treatment. Seven patients developed significant xerostomia, and four have cisplatin-related hearing loss requiring amplification. The early evidence of excellent response (89% pathologic complete response of primary sites; 78% complete response of nodal sites), coupled with acceptable treatment morbidity, warrants further study of this approach.

Squamous cell carcinoma: infiltrating monocyte/macrophage subpopulations express functional mature phenotype

Biopsies from 26 patients with advanced stage squamous cell carcinoma of the head and neck were investigated to determine the intensity of the inflammatory cellular infiltrate and the expression of leucocyte antigens. Mononuclear cell infiltration varied considerably between the individual patients and also within the tumour. Tumour-infiltrating cells consisted mainly of T lymphocytes and monocytes (Mo)/macrophages (M phi). Staining procedure with monoclonal antibodies (moabs) against Mo/M phi revealed different clusters of antigen expression: (1) moabs 27E10 and a-CD35 detected a subgroup of Mo/M phi with particular staining of perivasal Mo; (2) moab a-CD1 stained preferentially cells in tumour cell clusters; (3) moabs that reacted with cells of either typical M phi or dendritic morphology throughout the tumour-tissue: a-Fc gamma receptor I-III, a-class II antigens, a-CD4, Rm3/1, a-CD36 and 25F9. Thus, the majority of tumour-infiltrating mononuclear phagocytes were found to possess a rather mature phenotype. The number of Mo/M phi with mature phenotype within the tumours correlated with T lymphocyte infiltration in the tissue.