Glassy cell carcinoma of the uterine cervix responsive to neoadjuvant intraarterial chemotherapy

Described as a poorly differentiated adenosquamous cancer, glassy cell carcinoma of the uterine cervix is a rare disease considered to have an extremely poor prognosis. Saitama Medical Center has been offering neoadjuvant intraarterial chemotherapy (NAC) to cervical cancer patients as a means of avoiding postoperative radiation therapy, achieving downstaging, and improving prognosis. We report a patient with glassy cell carcinoma of the uterine cervix who responded to NAC, and we discuss this case with reference to reports in the literature. A 28-year-old gravida 1, para 0 patient was referred to the Department of Obstetrics and Gynecology at Saitama Medical Center for concurrent cervical cancer at 23.5 gestational weeks. The patient was admitted to our center following the diagnosis of stage IIb cervical cancer (glassy cell carcinoma), to await fetal development, and an elective cesarean section was performed at slightly more than 29 gestational weeks. Three cycles of NAC with carboplatin (CBDCA)/etoposide/epirubicin, started 3 days after the operation, shrank the tumor remarkably. An extended radical hysterectomy was subsequently performed. It has been 6 years, to date, since the initial treatment, and our patient is alive and disease/recurrence free.     

Advanced gastric carcinoma successfully treated with TS-1 as neoadjuvant chemotherapy

We report a patient with advanced gastric carcinoma successfully treated with the novel oral fluoropyrimidine anticancer drug TS-1 as neoadjuvant chemotherapy. The patient was a 76-year-old man who had gastric cancer clinically diagnosed as N2T4, invading the pancreas, the duodenum, and the transverse colon. He was treated as an outpatient with TS-1, 120 mg, administered orally every day for 28 days, followed by 14 days' rest, as one course. Two courses resulted in a marked reduction of the tumor without severe toxicity. Subsequently, the patient underwent curative surgery consisting of distal gastrectomy with D2 lymph node dissection. No surgical complications were observed. On microscopic examination, a few tumor cells were detected in the ulcer scar of the resected stomach and in the regional lymph nodes. Our report is the first to demonstrate the advantages of TS-1 as neoadjuvant chemotherapy for the treatment of advanced gastric carcinoma. Received: July 6, 2000 / Accepted: October 4, 2000     

胃小细胞癌五例临床病理分析

目的观察胃小细胞癌的临床及病理形态特点以探讨其组织发生及预后。方法对５例胃小细胞癌进行光镜观察,并对全部病例做组化及免疫组化染色,组化为Ｇｒｉｍｅｌｉｕｓ染色,标记物为ＮＳＥ,ＣｇＡ。结果胃小细胞癌组织学形态、生物学行为酷似肺小细胞癌,Ｇｒｉｍｅｌｉｕｓ染色有８０％病例瘤细胞胞浆内有嗜银颗粒,免疫组化证实其对ＮＳＥ,ＣｇＡ有一定敏感性,阳性率分别６０％,８０％。随访显示胃小细胞癌平均生存期为６个月。结论胃小细胞癌组织发生可能来源于弥散的神经内分泌细胞,属高度恶性肿瘤,预后较差。     

Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study

Background. Patients with locally advanced gastric cancer (cT3, cT4, N+, M0) have a dismal prognosis, despite complete resection. The objective of this study was to evaluate the toxicity and efficacy of neoadjuvant chemotherapy using the PLF (cisplatin/leucovorin [folinic acid]/5-fluorouracil [FU]) regimen in these patients. Primary endpoints of the study were the toxicity and the response to chemotherapy. Secondary endpoints were the rate of complete resection, survival, and first site of failure. Methods. Forty-nine patients with adenocarcinoma of the stomach were enrolled. Staging was based on abdominal computed tomography (CT) scans, endosonography, and laparoscopy. The intention was to administer two cycles (each containing six courses) of preoperative chemotherapy, consisting of cisplatin 50mg/m², high-dose folinic acid (HD-FA) 500mg/m², and HD 5-FU (HD-5-FU) 2000mg/m² (PLF). Following chemotherapy all patients were referred to surgery. To be evaluable for response, survival, and first site of failure, the patient had to receive at least one cycle of chemotherapy. Results. Toxicity observed was low, with grade 3 toxicity in fewer than 5% of the patients and two events of grade 4 toxicity (diarrhea and pulmonary embolism). Forty-two of the patients (86%) received at least one cycle of chemotherapy. The clinical response rate in these patients was 26% (11/42 patients). In 76% of the patients (32/42), a complete resection was possible. The median duration of follow-up for the surviving patients was 58 months (range, 38 to 80+ months). The median survival time for the 42 patients assessable for response was 25.4 months (range, 6 to 80+ months). After complete resection, median survival time was 32 months (range, 7.6 to 80+ months). The median survival time for clinically responding patients has not yet been determined, but 5-year survival is 90%. Twenty of the 32 completely resected patients (62.5%) had recurrences. First site of failure was peritoneal dissemination in 10 patients; locoregional and distant recurrences were rare. Conclusion. Neoadjuvant chemotherapy with PLF in patients with locally advanced gastric cancer has low toxicity and reasonable efficacy, allowing administration on an outpatient basis. Clinically responding patients have an excellent outcome after complete resection. The development of peritoneal dissemination even after neoadjuvant chemotherapy and complete resection remains an unsolved problem in patients with nonintestinal type tumors.     

Inhibitory effect of neoadjuvant chemotherapy on metastasis of oral squamous cell carcinoma in a mouse model

The presence or absence of metastasis bears an important influence on the prognosis of head and neck cancer patients. Neoadjuvant chemotherapy has become widely employed as an initial treatment. However, the actual effectiveness of neoadjuvant chemotherapy on metastasis is still unestablished. Therefore, using an orthotopic implantation model in which cervical lymph node metastasis of oral squamous cell carcinoma can be reproduced, we investigated the inhibitory effect of neoadjuvant chemotherapy on metastasis. A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19 cells, was implanted into the tongues of nude mice. After implantation, the mice were divided into four groups: S (surgery), C + S (preoperative chemotherapy + surgery), S + C (surgery + postoperative chemotherapy), and a control (nontreatment) groups. The treatment (tumor resection or chemotherapy) was started 7 days postimplantation. The effects of each treatment on cervical lymph node metastasis were investigated by examining the rate of lymph node metastasis formation at 28 days postimplantation. In the control group, five of the 11 mice died of cachexia before the end of the experiment. However, all mice in the S, C + S, and S + C groups survived until 28 days after implantation. The cervical lymph node metastasis rates were 81.8% in S, 18.1% in C + S, 63.6% in S + C, and 100% in control groups. Thus, metastasis to the cervical lymph node was markedly inhibited by the combination of neoadjuvant chemotherapy and tumor resection. The findings of this study indicate that neoadjuvant chemotherapy is effective for inhibiting metastasis, and that it is necessary to begin chemotherapy as early as possible to achieve an inhibitory effect on metastasis. Considering these effects, if anticancer drugs are used, better therapeutic results can be expected.     

A case of mucinous carcinoma of the breast that demonstrated a good pathological response to neoadjuvant chemotherapy despite a poor clinical response

A 30-year-old woman presented with a right breast tumor. Mucinous carcinoma was diagnosed by core needle biopsy (T2: 5 cm N1 M0). Despite receiving a neoadjuvant anthracycline and taxane regimen, the patient demonstrated no clinical response (NC). Based on the patient's strong preference, we performed breast-conserving surgery. On histological examination, we observed widespread mucus and a few viable malignant cells, a Grade 2 therapeutic response. Neither optimal management procedures nor guidelines for chemotherapy for primary mucinous carcinoma of the breast have been established. It is a reasonable assumption, however, that discordance between the clinical response and therapeutic response to neoadjuvant chemotherapy may occur in cases of mucinous carcinoma.     

Molecular biomarkers to predict response to neoadjuvant chemotherapy for bladder cancer

Cystectomy is the gold standard for treatment of localized muscle-invasive bladder cancer. However, about 50% of patients develop metastases within 2 years after cystectomy and subsequently die for the disease. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival in patients with muscle-invasive bladder cancer, and pathological response to neoadjuvant treatment (downstaging to ⩽pT1 at cystectomy) is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from neoadjuvant therapy. The identification of reliable biomarkers that could enable the clinicians to identify patients who will really benefit from neoadjuvant chemotherapy is a major issue. This approach could lead to individualized therapy, in order to optimize the chance of response, avoiding the impact of neoadjuvant treatment on quality of life and the delay of cystectomy in non-responder patients. However, no molecular predictive biomarkers have shown clinical utility.This paper aims to review currently available data about biomarkers predictive of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.     

A pilot study of adjuvant chemotherapy with irinotecan and cisplatin for completely resected high-grade pulmonary neuroendocrine carcinoma (large cell neuroendocrine carcinoma and small cell lung cancer)

Background

Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high-grade neuroendocrine carcinomas (HGNEC) of the lung. In patients with completely resected HGNEC, platinum-based adjuvant chemotherapy may be considered. However, the optimum chemotherapy regimen has not been determined. We conducted a multicenter single-arm phase II trial to evaluate irinotecan and cisplatin in postoperative adjuvant chemotherapy for HGNEC patients.

Patients and methods

Patients with completely resected stage I–IIIA HGNEC received four cycles of irinotecan (60 mg/m², day 1, 8, 15) plus cisplatin (60 mg/m², day 1). This regimen was repeated every 4 weeks. The primary endpoint was the rate of completion of chemotherapy (defined as having undergone three or four cycles), and secondary endpoints were the rate of 3-year relapse-free survival (RFS), rate of 3-year survival and toxicities.

Results

Forty patients were enrolled between September 2007 and April 2010. Patients’ characteristics were: median age (range) 65 [45–73] years; male 85%; ECOG-PS 1 60%; LCNEC 57% and SCLC 43%; stage IA/IB/IIB/IIIA 32/35/8/5%; 95% received lobectomy. The rate of completion of chemotherapy was 83% (90% C.I.; 71–90%). The rate of overall survival at 3 years was estimated at 81%, and that of RFS at 3 years was 74%. The rates of overall survival and RFS at 3 years were 86 and 74% among 23 LCNEC patients, and 74 and 76% among 17 SCLC patients, respectively. Nineteen patients (48%) experienced grade 3 or 4 neutropenia, but only five patients (13%) developed febrile neutropenia. Two patients (5%) developed grade 3 diarrhea, and four patients (10%) had grade 3 nausea. No treatment-related deaths were observed in this study. All 40 specimens were also diagnosed as HGNEC by central pathological review.

Conclusions

The combination of irinotecan and cisplatin as postoperative adjuvant chemotherapy was feasible and possibly efficacious for resected HGNEC.     

Glutathione-associated enzymes in head and neck squamous cell carcinoma and response to cisplatin-based neoadjuvant chemotherapy

Glutathione S-transferases (GSTs) are metabolic phase II enzymes that promote reactive metabolite elimination by conjugating them to glutathione (GSH). Because of their important role in xenobiotic metabolism and detoxification, they have been implicated in carcinogenesis processes, especially epithelium transformation. Moreover, their influence on response to chemotherapy in cancer patients has been demonstrated. Genetic polymorphisms for GSTM1, GSTT1 and GSTP1 have been found in human populations and have been shown to have phenotypic consequences. To investigate the role of GST enzymes in carcinogenesis and in response to chemotherapy in patients with head and neck squamous cell carcinoma (HNSCC), GSTP1, GSTM1 and GSTT1 were studied prospectively in a large series of HNSCC patients. Correlations between GST alterations, p53 mutation status and clinical response to chemotherapy were investigated. We showed that the risk of developing laryngeal cancer was increased by 2.6-fold [95% CI 1.6--6.1] in patients with the GSTM1 null genotype and by 2.8-fold [95% CI 0.9--8.1] in patients with the homozygous GSTP1 val105 genotype. Furthermore, individuals with this latter genotype were over-represented in the p53 mutation group (p = 0.05). After storage duration and hemolysis adjustment, a significantly lower plasmatic GSTP1 level was observed in complete responders compared with partial and non-responders (mean: 4.4 +/- 0.06 microg/l, 4.7 +/- 0.06 microg/l and 4.7 +/- 0.07 microg/l; p = 0.05), respectively. The prevalence of p53-mutated tumors was significantly higher in the group of non-responders (81%) compared with partial (60%) and complete responders (64%) (p = 0.05). Two types of multivariate analysis were performed including parameters that have been shown to influence response to chemotherapy significantly in univariate analysis. p53 mutations and high tumor stage are independent factors of non-response to chemotherapy, whereas plasmatic GSTP1 levels and low tumor stage are independent factors of complete response. Our data suggest that GST enzymes are associated with larynx cancer and that their use as predictive factors and treatment targets should be further explored.     

新辅助化疗对围手术期非小细胞肺癌患者的影响

目的 研究新辅助化疗(MVP)是否影响非小细胞肺癌患者围手术期的安全性。方法 所有患者化疗方案均为MVP，即丝裂霉素(MMC) 长春碱胺(VDS) 顺铂(DDP)。将接受2周期术前新辅助化疗、根治性手术和2次术后化疗的患者与接受同样手术和4次术后化疗的患者进行比较。结果 在107例符合要求的病例中，新辅助化疗组有66例，对照组有41例，两组在性别、年龄、肿瘤分期、病理类型上均无统计学差异。新辅助化疗组患者的手术时间(P=0．262)、术中失血量(P=0．704)、术中输血量(P=0．811)、输血总量(P=0．074)比对照组患者略高，术后总引流量(P=0．061)稍低，但其差异均无统计学意义。两组术后死亡率(P=0．674)和并发症：心律失常(P=0．608)、支气管胸膜瘘(P=0．378)、肺炎(P=0．622)、呼吸衰竭(P=0．285)的比较亦均无统计学意义。结论 新辅助化疗对非小细胞肺癌患者围手术期的安全性无显著影响。     

A pilot study of neoadjuvant chemotherapy with mitomycin C,etoposide, cisplatin,and epirubicin for adenocarcinoma of the cervix

Background To evaluate the efficacy and toxicity of the combination of mitomycin C, etoposide, cisplatin, and epirubicin (MEPA) as neoadjuvant therapy for patients with cervical adenocarcinoma.Methods Fourteen patients with cervical adenocarcinoma received neoadjuvant MEPA therapy followed by radical hysterectomy. The International Federation of Gynecology and Obstetrics stage was: IB1 in 2 patients, IB2 in 5, and IIB in 7. The MEPA regimen consisted of mitomycin C (15mg/m²) on day 1, etoposide (70mg/m²) on days 1 to 3, cisplatin (15mg/m²) on days 1 to 5, and epirubicin (30mg/m²) on day 1, with this course being repeated every 4 weeks. After two or three courses of chemotherapy, all patients underwent radical hysterectomy. Postoperative radiotherapy was given to 6 patients who showed risk factors at surgery.Results Of the 14 patients, 7 had complete remission (CR) clinically, 6 had partial remission, and only 1 showed no change. Examination of surgical material revealed no residual disease in 6 patients, and microscopic residual disease (5mm) in 2 patients. The patients who had no residual disease or microscopic disease in their hysterectomy specimens showed a significantly longer survival than those with macroscopic residual disease (P = 0.012). The dose-limiting toxicity was myelosuppression. Of the 33 treatment cycles administered, leukopenia of grade 3 or more occurred in 70%, and thrombocytopenia of grade 3 or more occurred in 79%. There were no therapy-related deaths.Conclusion Although severe myelosuppression was also observed, there was a satisfactory response rate to MEPA therapy, which showed a good pathological CR rate.     

联合化疗加放射治疗局限期小细胞肺癌

回顾性分析局限期小细胞肺癌６０例，ＡＤＭ、ＤＤＰ、ＶＰ－１６、ＣＴＸ联合化疗加胸部（６０）Ｃｏ放疗，ＤＴ５０～６０ＧＹ／６～７周。放疗结束后２个月左右复查，将获得ＣＲ的４９例，采用随机分组分为预防性全脑照射组（ＰＣＩ）２５例及对照组２４例。结果为生存时间与ＫＰＳ计分和ＣＥＡ值明显相关，而与是否行脑预防照射无明显差异。     

新辅助化疗在老年中晚期口腔鳞状细胞癌治疗中的临床意义

目的：探讨分析新辅助化疗在治疗老年中晚期口腔鳞状细胞癌中的临床效果。方法收集46例老年中晚期口腔鳞状细胞癌行新辅助化疗患者作为研究组,选取同期收治的60例未行新辅助化疗老年中晚期口腔鳞状细胞癌患者作为对照组,统计入组患者新辅助化疗后临床有效率、病理有效率,对比新辅助化疗前后细胞凋亡及增殖指数,肿瘤组织Ki-67、EGFR、p53及RARβ的表达变化,并分析新辅助化疗后手术及生存情况,比较两组生存率差异。结果研究组化疗后临床有效率和病理有效率分别为80.43%和69.57%。化疗后细胞凋亡指数明显高于化疗前,细胞增殖指数低于化疗前,差异均具有统计学意义（P=0.007、0.015）。化疗后Ki-67、EGFR、p53均低于化疗前,RARβ高于化疗前,差异均具有统计学意义（P=0.004、0.027、0.021、0.013）。研究组患者的中位生存期为28个月,新辅助化疗3、4个疗程患者远期生存率高于2个疗程患者,差异有统计学意义（P=0.021、0.017）。3个疗程和4个疗程化疗患者远期生存率比较差异无统计学意义（P=0.117）。对照组患者中位生存期为17个月,两组患者生存率差异具有统计学意义（P=0.015）。结论新辅助化疗可从多方面改善老年中晚期口腔鳞状细胞癌的临床效果,应成为其综合治疗的重要组成部分。     

彩色多普勒超声对乳腺癌新辅助化疗疗效的评价

目的探讨彩色多普勒超声对评价乳腺癌新辅助化疗疗效的价值。方法48例患者51处病灶在新辅助化疗前后分别对原发灶及腋下淋巴结进行观察。以化疗前彩超体积测量比手术前肿瘤体积缩小>50%为化疗有效,分析化疗有效与化疗无效肿瘤在新辅助化疗前后原发灶内血流分级及Vmax、RI值的变化。结果36处乳腺癌化疗有效;其原发灶内血流信号分级降低或血流消失;Vmax、RI值降低(P<0.01);化疗前发现异常淋巴结共40例,化疗后有34例缩小或消失,30例血流丰富程度明显降低或消失。结论彩色多普勒超声是对乳腺癌新辅助化疗进行疗效评价的客观而有效的检测工具,其Vmax、RI值可作为潜在预测乳腺癌新辅助化疗疗效的敏感指标。     

双时相99mTc-MIBI SPECT/CT显像预测局部晚期鼻咽癌对含多西他赛新辅助化疗敏感性的价值

背景与目的：在局部晚期鼻咽癌的治疗中,含多西他赛新辅助化疗正得到广泛的应用,其可能进一步提高局部晚期鼻咽癌的生存率。如果能在化疗前预测鼻咽癌对含多西他赛新辅助化疗的敏感性,将有助于更合理地为鼻咽癌患者制定个体化的治疗方案。前期研究发现,^99mTc-MIBI显像能够预测鼻咽癌对经典的顺铂联合5-氟脲嘧啶(5-FU)的化疗敏感性,但^99mTc-MIBI显像对含多西他赛方案化疗敏感性的预测价值有待进一步探讨。本研究的目的是探讨双时相^99mTc-MIBI SPECT/CT显像预测局部晚期鼻咽癌对含多西他赛新辅助化疗敏感性的价值。方法：31例局部晚期鼻咽癌患者,分别于注射^99mTc-MIBI后即刻和2 h后进行早期和晚期^99mTc-MIBISPECT/CT显像。所有患者行2个疗程TPF方案(多西他赛+顺铂+5-FU)新辅助化疗。分析^99mTc-MIBI SPECT/CT显像中早期摄取率、晚期摄取率和清除率与新辅助化疗的疗效关系。结果：根据磁共振评价新辅助化疗疗效,化疗高反应病灶的早期摄取率为2.67±0.83,而化疗低反应病灶的早期摄取率为1.69±0.46,差异有统计学意义(P=0.003);晚期摄取率分别为1.46±0.39和1.06±0.62,差异有统计学意义(P=0.026)。清除率在化疗高反应病灶(44.9%±13.9%)和化疗低反应病灶(35.5%±30.5%)之间的差异无统计学意义(P=0.23)。ROC曲线分析,早期摄取率AUC=0.84,最佳诊断界点为1.97,其灵敏度为74.2%,特异度为87.5%,阳性预测值为95.8%,阴性预测值为46.7%,准确率为76.9%。结论：^99mTc-MIBI SPECT/CT显像早期摄取率和晚期摄取率能够预测局部晚期鼻咽癌对含多西他赛方案新辅助化疗的敏感性。     

Predictive markers of response to neoadjuvant chemotherapy in breast cancer

Several randomized prospective studies on breast cancer patients have proved the safety of neoadjuvant chemotherapy. These trials have also demonstrated that tumor down staging does indeed improve the eligibility for breast conservative surgery without increasing local recurrence rates with possibly an improved survival. However, complete pathologic remissions are noted in only 3–30% of patients. About 20% of patients do not benefit from different chemotherapy regimens currently in use and are thus subjected to toxic drugs. This often leads to progression of disease and thereby the surgeon may lose a window of opportunity to obtain durable locoregional control of disease. Identification of predictive markers associated with pathologic complete response can help to distinguish patients with high or low probability of a response to treatment so that an individualized treatment plan can be implemented. It could also streamline the development of new alternative regimens for those who are unlikely to benefit from existing drugs. It is expected that a combination of markers will be more informative than a single one. So far, several factors have been studied as predictors for response to cytotoxic treatment, viz., tumor size, hormone (estrogen and progesterone) receptor status, tumor type and differentiation, HER2/cerB-2, tumor proliferation Ki-67, apoptosis related genes p53, bcl-2 and BAX; certain subgroups of breast cancer, and the latest in this category is gene expression profiling. However, in terms of prediction of drug responsiveness, data reported are still very limited.This review aims to discuss the current relevant literature on the subject.     

Integration of chemotherapy and radiation therapy for small cell carcinoma of the lung

Two chemotherapy trials using cyclophosphamide, doxorubicin hydrochloride and high-dose vincristine sulfate with or without methotrexate have induced a 93% incidence of complete remission in limited disease presentation of small cell bronchogenic carcinoma of the lung and 39% incidence in extensive disease. The first trial without consolidation radiotherapy had a local failure rate of 65%, which dropped to 17% with consolidation radiotherapy to the primary and mediastinum. Prophylactic whole brain radiotherapy prevented local recurrence in 98% of evaluable patients. One carcinomatous meningitis and 5 intraspinal recurrences were noted among the 38 patients in the CAV-M trial. We conclude that high-dose vincristine sulfate is associated with an improved incidence of complete remission; that prophylactic whole brain radiotherapy has been highly successful; that prevention of intraspinal recurrence will necessitate the use of craniospinal axis radiation therapy and consolidation radiation therapy improves local control of primary and mediastinum.     

Locally advanced anal small cell carcinoma with durable complete response to chemoradiation followed by consolidation chemotherapy: case report and literature review

Extrapulmonary small cell carcinoma (EPSCC) is a rare and aggressive clinical entity that can involve a variety of anatomic locations, including the gastrointestinal tract. Involvement of the gastrointestinal tract is associated with a particularly poor prognosis with patients often presenting with widespread dissemination on initial clinical presentation or rapidly progressing to systemic disease from locoregional involvement. Primary small cell carcinoma of the anal canal is extremely rare, with limited published case reports in the literature. As a result, management of this disease is not well defined, and outcomes are poor with high rates of disease relapse. We report a patient with locally advanced anal small cell carcinoma after presenting with irregular bowel movements, changes in stool caliber, and rectal bleeding for two months and achieved a durable complete response to concurrent chemoradiation with cisplatin and etoposide followed by consolidation chemotherapy and discuss our current understanding of this disease. Specifically, we review the epidemiology, risk factors, clinical course, the treatment strategies over the past two decades, and prognosis for EPSCC. Finally, we conclude our discussion by reviewing the rationale of our treatment regimen and the potential role and benefit of consolidation therapy in the management of this rare and aggressive disease.     

Control of cell proliferation kinetics of tumor in neoadjuvant chemotherapy for advanced oral squamous cell carcinoma and its prognostic implications

Background. Few attempts have so far been made at studies of the cell proliferation kinetics of the tumor in neoadjuvant chemotherapy for head and neck cancer. We examined the effects of neoadjuvant chemotherapy for advanced oral squamous cell carcinoma in terms of the cell proliferation kinetics of the tumor, and attempted to correlate them with patients' survival. Methods. Fifty-two patients with advanced oral squamous cell carcinoma who received neoadjuvant chemotherapy followed by surgery participated in this study. Cellular DNA content and mitotic index (MI) in tissue samples were measured before and after chemotherapy, using a cell image analyzer. Results. A decrease in both mean DNA content (mean DNA) and MI (left-shift type of change in cell growth kinetics), indicating an accumulation of cancer cells in the G0-G1 phase, was found in 25 patients. An increase in mean DNA with decreased MI (right-shift type), which was found in 13 patients, appeared to be correlated with an accumulation of cancer cells in the S-G2 phase. Neither of these two types of change, which were considered to be a favorable effect, were found in 14 patients (ineffective type). Excellent survival rates were obtained in patients who showed favorable changes in cell growth kinetics (79% for patients with left-shift type and 92% for patients with right-shift type), whereas the survival rate for patients with the ineffective type was extremely poor (14%). The type of change in cell proliferation kinetics was a powerful independent prognostic indicator. Conclusion. Analysis of cell growth kinetics appears to be useful not only as a diagnostic tool to predict patient outcome but also as a means to infer the chemotherapeutic effects in oral squamous cell carcinoma. Received: January 10, 2002 / Accepted: February 27, 2002