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PubMedDate not supplied

Sequential and/or concurrent hypofractionated radiotherapy and concurrent chemotherapy in neoadjuvant treatment of advanced adenocarcinoma of the pancreas. Outcome and patterns of failure.

BACKGROUND/AIMS: To investigate treatment outcome and patterns of failure of sequential chemotherapy (CHT) and/or concurrent hypofractionated radiotherapy (RT) and CHT followed by surgery in locally advanced non-metastatic pancreatic adenocarcinoma. METHODOLOGY: Seven patients with locally advanced but marginal resectable tumors (close contact but no signs of infiltration of the mesenteric vessels and/or vena portae) were treated with hypofractionated RT (5x3 Gy per week) and concurrent continuous infusion (300 mg/sqm/24 h, 7 days per week) of 5-fluorouracil (FU). Ten patients with locally advanced disease with radiologically suspected infiltration of the mesenteric vessels and/or v. portae were treated with 2 cycles of Cisplatin (75 mg/sqm) and Gemcitabine (2x1250 mg/sqm), and patients without tumor progression received the same concurrent RT/CHT as group 1. Four weeks after RT/CHT radical pancreatectomy was planned for patients with stable disease or remission. RESULTS: Toxicity was low in both groups, with no CTC grade 4 toxicity. In group 1, RT/CHT was completed in all patients. There was no radiological remission, but stable disease in 5 out of 7 patients. All 5 patients underwent resection of the primary tumor with a R0-resection in 3 patients. In group 2, 8 patients completed CHT and RT/CHT treatment as planned. There were 3 with partial remission. Operation was done in 4 patients, but only one R0 resection was achieved. The median survival time for all 17 patients is 13 months, with 1- and 2-year survival being 53% and 18%, respectively. Local progression was observed in 9, peritoneal seeding in 7 and distant metastasis (mostly liver and lung) in 8 patients. CONCLUSIONS: The neoadjuvant therapy could be administered with low toxicity. Results of this study warrant further investigation aiming at optimal tailoring in of this treatment approach in these two subgroups of patients.

Adenocarcinoma↗

PubMedDate not supplied

Chemotherapy of advanced and recurrent cervical carcinoma.

Chemotherapy is used primarily to treat advanced or recurrent cervical cancer. There are three major applications: primary therapy, as a radiation sensitizer, and neoadjuvant therapy. Primary chemotherapy is employed in advanced and disseminated cervical carcinoma (Stage VB). The four best single drugs with moderate activity against cervical cancer are: cisplatin, ifosfamide, dibromodulcitol (mitolactol), and Adriamycin (doxorubicin). Cisplatin and ifosfamide appear to be the best combination therapy: they provide an objective response rate of 33%. However, because the overall survival was not significantly improved with combination therapy, single-agent therapy with one of the above active drugs is acceptable. For stages IIB, III and IVA, the primary therapy is still radiation. Concomitant chemotherapy with hydroxyurea or a combination of cisplatin and 5-fluorouracil (5-FU) have been shown to enhance radiation response in several randomized trials. Hydroxyurea is the preferred radiation sensitizer because it offers less toxicity, ease of administration, and equivalent results. Chemotherapy in neoadjuvant setting produces promising results. Various cisplatin combinations of mitomycin C, 5-FU, vincristine, and bleomycin have been employed to shrink locally advanced cervical cancer and permit safe, radical excision. Early results with these combinations in small trials are encouraging but further studies are needed to fully evaluate their potential.

Antineoplastic Agents↗

PubMed2005

The value of serial arteriography in osteosarcoma: delivery of chemotherapy, determination of therapy duration, and prediction of necrosis.

PURPOSE: To investigate the value of serial arteriography to assess tumor response, predict necrosis, and individualize the duration of a combined intravenous (IV) and intraarterial (IA) neoadjuvant chemotherapy protocol in patients with biopsy-proven high-grade osteosarcoma or malignant fibrohistiocytoma of bone. MATERIALS AND METHODS: Between July 1987 and March 2003, 109 patients completed a chemotherapy protocol of neoadjuvant IV doxorubicin and IA cisplatin. Patients were eligible regardless of age, disease stage, or disease site. A minimum of three IA cycles followed by definitive surgery was required for inclusion in the final analysis. IA dose and duration were increased for tumors larger than 10 cm. Initial arteriograms were scored as indicating mild, moderate, or marked tumor neovascularity (TNV). Subsequent arteriograms were prospectively compared with the baseline image for percent change in TNV. Treatment continued until a maximum of five cycles were administered or one of three criteria were met: (i) at least 90% decrease in TNV, (ii) plateau of effect, or (iii) no response. RESULTS: Of 408 IA procedures, 42 patients underwent three cycles, 53 underwent four, and 14 required five cycles of neoadjuvant therapy. There was a 2.5% minor complication rate. Eighty-six percent of patients exhibited at least 90% decrease in TNV and 82% exhibited good histologic response (> or =90% tumor necrosis). Serial arteriography predicted a good histologic response with an accuracy of 90% and a sensitivity of 97%. CONCLUSIONS: Serial arteriography was highly sensitive and accurately predicted good responses. This individually modified, dose-intensified neoadjuvant protocol yielded an excellent histologic response rate with minimal complications. Future endeavors should involve a multiinstitutional study of this unique approach.

Adolescent↗

PubMed2006

The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment.

Total mesorectal excision (TME) refers to the surgical removal of the complete perirectal soft tissue envelope, using sharp instruments under direct vision, and has become the contemporary standard of care for patients with rectal cancer. Pathologists play a key role in the evaluation of these specimens, including the quality assurance of surgical performance, as well as evaluation of the circumferential radial margin (CRM). While the latter is the most significant predictor of local recurrence, the quality of the excised mesorectum is another important factor in assessing the risk of local recurrence in patients with a negative CRM. Since proper pathological assessment of the TME specimen provides important prognostic information, as well as critical feedback to surgeons regarding technical performance, it is important to have adequate guidelines for the macroscopic handling of these specimens. The CLASSICC study of the Medical Research Council in the United Kingdom, as well as the Dutch TME trial have introduced a new standard for the pathological assessment of TME specimens, including an approach that involves assessment in both the fresh and fixed states, at least 48 hours of fixation of an intact specimen, with observations made on both the external appearance and cross-sectional slices. This article reviews the pathological assessment of the TME specimen, including basic definitions, current international guidelines, an approach to evaluating the mesorectum and a discussion of special issues relating to margins, lymph node retrieval and effects of neoadjuvant therapy.

Digestive System Surgical Procedures↗

PubMed2000

[Preoperative downstaging in advanced stomach carcinoma. Wishful thinking or reality].

By the time it is diagnosed, gastric carcinoma is usually already advanced and, as a result, has a poor prognosis. Surgery, with complete (R0) resection of the tumor, is the only chance of cure for this disease. However, in locally advanced gastric carcinoma this is only possible in approximately half of all cases. In order to help improve the prognosis of patients with advanced stage carcinomas, the concept of multimodal therapy is presently being evaluated. The results of studies of postoperative adjuvant therapy have been contradictory, with the result that no indication for such treatment outside of study protocols presently exists. Recently, preoperative application of chemotherapy, the so-called "neoadjuvant" therapy concept, has become increasingly important, since it has been demonstrated that, in individual cases, tumors thought to be primarily unresectable have been able to be completely resected after chemotherapy. Based on the available studies, one can assume that, in a subgroup of patients with not yet identified favorable tumor biologic characteristics, a true down staging of the tumor occurs. To what extent a preoperative "over-staging" may be a factor can only be estimated statistically, since the presently available methods for clinical estimation of tumor stage are never as accurate as the final histopathologic evaluation. Since the recently started, randomized multicenter study under the auspices of the EORTC compares surgery alone with a combination of surgery and preoperative chemotherapy in locally advanced gastric carcinoma, information will soon be available which will help clarify the effectiveness of this therapy concept.

Gastrectomy↗

PubMed1999

[Value of tumor debulking in gastrointestinal tumors].

Tumor debulking of gastrointestinal tumors for the reduction of tumor mass is intended to improve subsequent treatment efficacy. However, in advanced malignant disease, this therapy is often associated with increased morbidity and lethality. Adjuvant therapies cannot be initiated when needed. Therefore, long-term survival remains unaffected. Advances in biomedical science provide preliminary explanations for these therapeutic problems. Modern therapeutic concepts like neoadjuvant therapy for locally advanced tumors are based on these findings. The probability of complete R0 resections, necessary to improve long-term survival, can be enhanced by these therapies. The ongoing prospective neoadjuvant studies for gastrointestinal tumors are already very encouraging.

Combined Modality Therapy↗

PubMedDate not supplied

[Leiomyosarcoma of the inferior vena cava: a case report].

Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare vascular tumour, with about 200 cases reported since 1871. The Authors report a case of leiomyosarcoma of the suprarenal inferior vena cava preoperatively diagnosed by ultrasonography and computed tomography. A surgical resection and venous wall reconstruction was performed. Complete surgical resection with a tumour-free margin (1 cm) is the treatment of choice. Neoadjuvant therapy may be given to downsize the tumour and increase resectability rate. When complete resection is not possible, debulking combined with radiation therapy provides good palliation.

Humans↗

PubMed2005

[Recent results of irinotecan therapy in colorectal cancer].

New results presented at ASCO Conference in 2003 added further important data to our knowledge on successful use of irinotecan in colorectal cancer (CRC). Irinotecan - just like oxaliplatin - given as neoadjuvant therapy with 5-FU - folinic acid (FUFA) can render originally unresectable liver or lung metastases of CRC resectable, giving the hope of long-term survival for a proportion of patients. Irinotecan combined with 5-FU is an essential part of the most successful palliative sequential chemotherapy of stage IV CRC. Sequential FOLFIRI before or after FOLFOX combination ensures the longest possible progression-free and overall survival for metastatic CRC patients in the palliative setting. In order to achieve the longest survival time, sequential use of both 5-FU, irinotecan and oxaliplatin is necessary. The French GERCOR Group achieved 26 months median overall survival with the sequential use of continuous infusional FUFA, oxaliplatin and irinotecan combinations in stage IV CRC. The analysis of large phase III trials using 5-FU, irinotecan and oxaliplatin revealed that the higher proportion of patients was treated with all three drugs, the longer overall survival was achieved. If applied with caution, toxicity and efficacy of irinotecan in elderly patients is not significantly different from that seen in younger population. The anti-VEGF bevacizumab increases the efficacy of first-line irinotecan therapy, while the addition of cetuximab restores irinotecan sensitivity in second line treatment of stage IV CRC. The combination of irinotecan with oral capecitabine is safe and effective in advanced CRC.

Antibodies, Monoclonal↗

PubMed1998

[Influence of neoadjuvant treatment on bladder infiltrating tumors treated with radical cystectomy].

Retrospective study of 107 patients diagnosed with infiltrant tumour of the bladder in stage T3-T4 N0-N1, treated with radical surgery. Eighty-four (84) received neoadjuvant therapy with radio- and/or chemotherapy. The neoadjuvant treatment was seen to provide significantly better survival, but the specific type of neoadjuvant treatment appears to have no influence. The multivariate study evidenced that the two most influential variables for survival are the complementary treatment and the clinical stage.

Actuarial Analysis↗

PubMed2006

Short-term preoperative radiotherapy in rectal cancer patients leads to a reduction of the detectable number of lymph nodes in resection specimens.

BACKGROUND AND AIMS: The Union Internationale Contre le Cancer and American Joint Committee on Cancer classification propose that pN(0)-classified colorectal lymphadenectomy specimens will ordinarily include 12 or more tumor-negative lymph nodes. We performed a clinical trial to investigate whether a short-term preoperative radiotherapy (5x5 Gy) leads to a reduction of the number of lymph nodes in rectal cancer specimens after total and partial mesorectal excision (TME and PME, respectively). MATERIALS AND METHODS: Within a 5-year period, 28 (15%) of 148 rectal cancer patients underwent hypofractionated preoperative radiotherapy in this monocenter study, whereas 120 patients (85%) underwent TME/PME surgery alone. The main criterion was the number of lymph nodes in TME/PME specimens. We used a stratified one-sided Wilcoxon-Mann-Whitney test to test for a significant difference in the number of lymph nodes, stratifying for tumor location and postoperative tumor stage. Patients who were suspected of having any alterations in the number of pelvic lymph nodes were excluded from the study. RESULTS: Fewer lymph nodes were detected in the TME/PME specimens of patients who received hypofractionated preoperative radiotherapy compared to patients who underwent TME/PME surgery alone (12 detectable lymph nodes vs 15; p=0.0005). Tumor location (p=0.095) and tumor stage (p=0.093) did not significantly influence the number of lymph nodes in this study. CONCLUSIONS: We conclude that a 5x5 Gy short-term preoperative radiotherapy leads to a reduction in the number of lymph nodes in TME/PME specimens. Because neoadjuvant therapy in rectal cancer for T(2) and T(3) tumors has advanced a new therapeutic standard procedure, in the future, less lymph nodes will be detected in TME/PME specimens. This might influence the required number of lymph nodes in current staging systems for rectal cancer in the future.

Combined Modality Therapy↗

PubMed2005

Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases.

BACKGROUND: The objective was to evaluate the effect of preoperative administration of newer chemotherapeutic agents (irinotecan and oxaliplatin) on development of steatohepatitis, which could limit surgical options. STUDY DESIGN: Thirty-seven patients were referred for resection of hepatic colorectal metastases. Thirteen patients received no neoadjuvant therapy (NO CHEMO group); 10 received neoadjuvant 5-fluorouracil only (5-FU group), and 14 received neoadjuvant irinotecan (n = 12), or oxaliplatin, or both (n = 4), in conjunction with 5-FU (IRI-OXALI group). Specimens were graded for the presence of nonalcoholic steatohepatitis (NASH) according to established criteria. Specimens were also evaluated by a nine-criteria liver injury score (LIS). RESULTS: Mean biopsy scores were: NO CHEMO: NASH, 1.2, LIS, 5.2; 5-FU only: NASH, 1.1, LIS 5.7; and IRI-OXALI: NASH, 1.9, LIS, 9.4. Biopsy scores were significantly worse for IRI-OXALI compared with NO CHEMO or 5-FU only for NASH score, p = 0.003, and close to significantly worse for LIS score, p = 0.057. A multivariate analysis showed that both being in the IRI-OXALI group and body mass index were independent risk factors for developing this type of steatohepatitis. CONCLUSIONS: Severe steatohepatitis can be associated with preoperative administration of irinotecan or oxaliplatin, especially in the obese. It can affect the ability to perform large liver resections. Consideration should be given to performing resections before commencing these agents and to obtaining preoperative biopsy in those who have received these agents.

Aged↗

PubMed1998

Effectiveness of preoperative radioactive iodine (131I) therapy for locally advanced papillary thyroid cancer: a case report.

We report here the effectiveness of preoperative radioactive iodine-131 (131I) therapy for locally advanced thyroid cancer. A 57-year-old woman demonstrated a hard neck tumor that markedly invaded the surrounding organs. The cytological diagnosis of the tumor using fine-needle aspiration biopsy was papillary carcinoma. Because curative resection of the tumor appeared difficult at her first visit, 131I therapy was performed prior to surgery and was more useful than expected. After 3 131I treatments, the tumor size was greatly reduced, and the patient underwent a curative operation. Histopathological diagnosis was well differentiated papillary carcinoma, pT4 and pN1b. The postoperative clinical course was uneventful. There have been no definitive reports using 131I as preoperative treatment for inoperable thyroid cancer. We suggest that 131I therapy may also be beneficial as neoadjuvant therapy for locally advanced thyroid carcinoma.

Biopsy, Needle↗

PubMed2006

Can rectal cancers with pathologic T0 after neoadjuvant chemoradiation (ypT0) be treated by transanal excision alone?

BACKGROUND: Patients with rectal cancer who have complete rectal wall tumor regression after neoadjuvant chemoradiation probably have eradication of tumor cells in the mesorectum as well, thus raising the possibility of transanal excision. METHODS: All pathology reports of all patients with locally advanced low and mid rectal cancer who underwent preoperative chemoradiation followed by radical resection from May 2000 to June 2004 were reviewed to evaluate the correlation between complete tumor response (ypT0) and nodal response. RESULTS: One hundred one consecutive patients had neoadjuvant chemoradiation followed by definitive operation. Four were excluded, leaving 64 men and 33 women (median age, 62 years). Fifty-three patients (55%) had mid rectal cancer, and 44 (45%) had low rectal cancer. Fifty-eight patients (60%) underwent low anterior resection, and 36 (37%) underwent abdominoperineal resection. In 17 patients (18%), no residual tumor cells were present within the rectal wall. One patient (6%) with ypT0 disease had positive lymph nodes. CONCLUSIONS: No residual tumor in the rectal wall correlates with the absence of viable cancer cells in the mesorectal tissue (94%). Approximately 10% of T1 tumors have involved lymph nodes, and local excision is an accepted option. Transanal excision could probably be considered in a highly selected group of patients with a mural pathologic complete response to neoadjuvant therapy. This approach should be prospectively investigated, and strict selection guidelines should be used.

Adult↗

PubMed1999

Non-small cell lung cancer: role of surgery for stages I-III.

Survival following surgical resection of non-small cell lung cancer (NSCLC) has improved since the 1960s, although the 5-year survival rate remains low. This article provides an overview of the role of surgery for NSCLC stages I-III, with a focus on optimizing long-term survival in those patients with resectable disease. Topics explored include diagnosis and staging, indications for resection, types of resection, and indications for adjuvant therapy. A review of the literature indicates a clear survival advantage for complete resection, and is suggestive of an advantage for mediastinal lymph node dissection (vs lymph node sampling) and neoadjuvant therapy (vs adjuvant therapy).

Carcinoma, Non-Small-Cell Lung↗

PubMed1992

[Advances in lung cancer].

Sessions about lung cancer of the 28th annual meeting of ASCO approached especially non small cell lung cancer (NSCLC). Undoubtedly the outstanding facts for this pathology was first the acknowledgment of the importance of a correct staging system, in particular in stage IIIA for which resection is a prognostic factor different for tumors T3N0, T3N1 as for N2. Two important topics have been discussed on therapy: stage IIIA treatment, in particular neoadjuvant therapy before surgery, and new drugs like Navelbine, taxol, and campthotecine which suggest the possibility of improvements for chemotherapy of NSCLC in the next few years. For small cell lung cancer (SCLC), different trials were designed to improve dose intensity with growth factors, fractionation of therapy, autologous bone marrow transplantation.

Antineoplastic Agents↗

PubMed1998

High-dose therapy for adult soft tissue sarcoma: dose response and survival.

The role for high-dose therapy in the treatment of sarcomas is controversial and limited. Numerous trials in soft tissue sarcomas have suggested dose-response relationships for doxorubicin (and epirubicin) and ifosfamide. Low doses of these agents are associated with lower response rates than aggressive doses that do not require cellular support. There is little evidence that doses high enough to require hematopoietic stem cell support achieve higher response rates. Complete responses remain rare, and no survival advantage has been documented. New drugs are needed urgently, particularly those with dose-response relationships and those achieving complete responses. In their absence, transplant therapy does not yet play a role in the treatment of soft tissue sarcomas, although further phase II trials could be performed to assess consolidation therapy for complete responders, patients requiring neoadjuvant therapy, and those with resectable oligometastatic disease. High-dose therapy has been evaluated more extensively in patients with pediatric histologies like Ewing's sarcoma, rhabdomyosarcoma, and osteosarcoma. Many more agents suited to transplant regimens have substantial activity against these histologies. Results from certain trials demonstrate improved, long-term, relapse-free survival compared with historical controls, whereas others suggest that selection biases may account for such "improvements." Development of new agents is needed. Carefully designed randomized trials to evaluate the role of high-dose therapy with cellular support should be strongly encouraged in these histologies.

Adjuvants, Immunologic↗

PubMed2000

Remission rates following preoperative chemotherapy and radiation therapy in patients with breast cancer.

PURPOSE: To evaluate remission and breast-conservation rates after preoperative chemotherapy or chemo-radiotherapy (CT-RT). PATIENTS AND METHODS: Seventy-three patients with 74 biopsy-proven invasive breast cancers prospectively entered the protocol. Eighteen patients were treated by neoadjuvant chemotherapy followed by surgery and adjuvant irradiation (chemotherapy group). Fifty-five patients with 56 tumors were treated with combined neoadjuvant chemo-radiotherapy, followed by surgery (chemo-radiotherapy group). Most patients of both treatment groups received 4 cycles of EC chemotherapy. In some patients with large tumors 3 cycles of CMF were added. Chemotherapy was followed by hormonal treatment with tamoxifen or LHRH agonists in case of positive hormone-receptor status. Preoperative radiotherapy was administered using 2 Gy fractions up to a total dose of 50 Gy, followed by a tumor boost of 6 to 11 Gy. The median overall treatment time was 41 days (range: 35 to 55 days). The median time interval between end of neoadjuvant therapy and surgery was 11 weeks (range: 10 to 22 weeks) and 27 weeks (range: 11 to 41 weeks) for the chemotherapy- and chemo-radiotherapy group. The median time interval between end of chemotherapy and the beginning of irradiation ranged between 2 and 8 weeks (median 4 weeks) in the chemo-radiotherapy group. RESULTS: Side-effects due to chemo- or radiotherapy were moderate and reversible. In the chemotherapy group 17/18 patients (94%) achieved a partial (pPR) and 1/18 patients (6%) a complete histopathological response (pCR). In the chemo-radiotherapy group 32/56 (57%) showed a pPR and 24/56 (43%) a pCR. The difference in complete remission is significant (Fisher's Exact Test: p = 0.004). In 45/74 cases (61%) the breast was preserved, immediate breast reconstructions with rectus myocutaneous flaps (TRAM) after mastectomy were performed in 8/74 cases (11%) and modified radical mastectomies without reconstruction were required in 21/74 cases (28%). The breast conservation rates were similar in both treatment groups. CONCLUSIONS: Even though the small number of patients in the present protocol does not permit definite conclusions, the results of combined modality treatment seem promising with regard to tumor remission within the treated breast and as a tool for breast conservation in advanced stage disease. On the basis of these encouraging data a prospective Phase-III study has been initiated.

Adult↗

PubMed2004

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer.

As an active and well-tolerated agent in the treatment of metastatic breast cancer, capecitabine (Xeloda, F. Hoffmann-La Roche, Basel, Switzerland) has the potential to confer significant clinical benefits in the primary treatment of breast cancer. The minimal myelosuppression and alopecia associated with capecitabine, together with its potential for synergistic activity with a range of other anticancer therapies, lend support to its use in combination regimens with other commonly used cytotoxic agents. Trials to date show that capecitabine combinations incorporating taxanes, vinorelbine, anthracyclines, and cisplatin are active and well tolerated in the metastatic setting. To more fully explore the clinical utility of capecitabine in early breast cancer, an extensive, worldwide phase II/III program is evaluating capecitabine as a component of adjuvant and neoadjuvant therapy. Results presented to date of the large adjuvant and neoadjuvant trials incorporating capecitabine are encouraging and suggest that women with breast cancer might benefit from the activity of capecitabine early in the disease course.

Antimetabolites, Antineoplastic↗