Postoperative adjuvant therapy for pancreatic cancer

The majority of patients diagnosed with pancreatic cancer present at an advanced stage, and only a small percentage are considered technically resectable at diagnosis. The overall prognosis for the majority is dismal, with a median survival in untreated cases of only 24 weeks. Even in resected patients the overall 5-year survival rate is generally only 5% to 10%; however, some reports indicate higher 5-year survival rates in patients treated with surgery who are pathologically staged with no lymph node involvement. Even when macroscopically complete resection is achieved, local recurrence (LR) rates are unacceptably high (30% to 70%), which is usually attributed to the difficulty of obtaining microscopically free surgical margins. Microscopic clearance is difficult to achieve because these tumors frequently extend into the peripancreatic tissues (e.g., retropancreatic fat), abut or invade the adjacent large vessels (the portal vein and superior mesenteric artery), and have a propensity to invade the lymphovascular and perineural space. Other common sites of failure after attempted curative resection include metastasis to the liver and the peritoneal cavity. Patients who present with pancreatic cancer, and for whom curative surgery is deemed possible, are thus potential candidates for adjuvant therapy because of the high local failure rate following resection alone. The radiotherapy dose that can be achieved in the postoperative setting for pancreatic cancer is limited because of the proximity of critical structures (e.g., the kidney, liver, small intestines, stomach, and spinal cord). Newer techniques such as conformal radiotherapy and intensity-modulated radiotherapy have the advantage of being able (theoretically) to precisely localize the dose to the target volume while reducing the dose to critical structures. These techniques may potentially enable the tumorcidal dose to be increased; however, they are only now becoming widespread. Systemic radiation-sensitizing chemotherapy is also a promising approach to take advantage of additive or synergistic effects with radiation locally, and for the sterilization of systemic disease. This concept of concomitant chemotherapy with radiotherapy, or chemoradiotherapy, has proved effective in a number of sites, including the anal canal, rectum, lung, and pancreas. The recent trials reviewed here varied considerably in terms of the total dose and technique used, and the choice of radiation sensitizing treatment.     

Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus

PURPOSE: Despite advances in microsurgical technique, many cavernous sinus meningiomas remain unresectable or only partially resectable, prompting referral of patients for radiation therapy. Stereotactic radiosurgery is recommended as therapy at some institutions. We evaluated our experience with fractionated radiotherapy to permit comparison with single-fraction radiosurgery. MATERIALS AND METHODS: Between July 1985 and January 1998, 21 women and 7 men were treated for primary (21) or recurrent (7) cavernous sinus meningiomas. Of these, 22 tumors were subtotally resected and 6 were unresectable. Of the 28 lesions, 26 were categorized histologically as benign (16), aggressive-benign (7), or malignant (3); 2 were not biopsied. All patients were treated with fractionated photon irradiation to a median dose of 53.1 Gy. We assessed prognostic factors for overall (OS) and progression-free survival (PFS), including age, gender, presentation (primary vs. recurrent), extent of surgical resection, radiotherapy dose, and technique. Influence of radiotherapy dose and technique on acute and late treatment toxicities was analyzed. RESULTS: One patient died of disease and 2 others were alive with progressive disease at last follow-up, yielding 8-year actuarial OS and PFS of 96% and 81%, respectively. Univariate analysis showed that none of the prognostic factors tested was significantly associated with OS or PFS. There were two late side effects of treatment: an orbital sac fibrosis and a 6-month decline of cognitive function documented by formal neuropsychiatric testing. Neither radiotherapy dose nor technique significantly influenced late toxicity. CONCLUSION: For unresectable or subtotally resected cavernous sinus meningiomas, fractionated radiotherapy provides patients with excellent progression-free survival and minimal treatment-related toxicity.     

Acute toxicity in definitive versus postprostatectomy image-guided radiotherapy for prostate cancer

PURPOSE: To assess the incidence of acute gastrointestinal (GI) and genitourinary (GU) injury and the dose-volume response in patients with clinically localized prostate cancer treated with image-guided radiotherapy using helical tomotherapy. METHODS AND MATERIALS: Between November 2004 and March 2007, 146 consecutive patients with localized prostate cancer were treated with helical tomotherapy at the City of Hope Medical Center. Of the 146 patients, 70 had undergone prostatectomy. Acute GI and GU toxicities were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Cancer of Medical scoring system. Events were scored for patients developing Grade 2 or greater morbidity within 90 days after the end of radiotherapy (RT). The dosimetric parameters included the minimal dose received by the highest 10%, 20%, 50%, 80%, and 90% of the target volume, the mean rectal dose, minimal rectal dose, maximal rectal dose, and the volume receiving > or =45, > or =65, and > or =70 Gy. These variables, plus the status of radical prostatectomy, hormonal therapy, RT techniques, and medical conditions, were included in a multivariate logistic regression analysis. A goodness-of-fit evaluation was done using the Hosmer-Lemeshow statistic. RESULTS: A dose-response function for acute GI toxicity was elicited. The acute GI Grade 2 or greater toxicity was lower in the definitive RT group than in the postoperative RT group (25% vs. 41%, p <0.05). Acute GU Grade 2 or greater toxicity was comparable between the two groups. No grade 3 or greater complications were observed. No dosimetric variable was significant for GU toxicity. For acute GI toxicity, the significant dosimetric parameters were the minimal dose received by 10%, 20%, and 50% of the target volume and the mean rectal dose; the most predictive parameter was the minimal dose received by 10% of the target volume. The dose-modifying factor was 1.2 for radical prostatectomy. CONCLUSION: The results of our study have shown that acute rectal symptoms are dose-volume related. Postprostatectomy RT resulted in a greater incidence of acute GI toxicity than did definitive RT. For postoperative RT, it would be prudent to use different dose-volume limits.     

Management of borderline resectable pancreatic cancer

Pancreatic cancer is the fourth most common cause of cancer death in the United States. Surgery remains the only curative option; however only 20% of the patients have resectable disease at the time of initial presentation. The definition of borderline resectable pancreatic cancer is not uniform but generally denotes to regional vessel involvement that makes it unlikely to have negative surgical margins. The accurate staging of pancreatic cancer requires triple phase computed tomography or magnetic resonance imaging of the pancreas. Management of patients with borderline resectable pancreatic cancer remains unclear. The data for treatment of these patients is primarily derived from retrospective single institution experience. The prospective trials have been plagued by small numbers and poor accrual. Neoadjuvant therapy is recommended and typically consists of chemotherapy and radiation therapy. The chemotherapeutic regimens continue to evolve along with type and dose of radiation therapy. Gemcitabine or 5-fluorouracil based chemotherapeutic combinations are administered. The type and dose of radiation vary among different institutions. With neoadjuvant treatment, approximately 50% of the patients are able to undergo surgical resections with negative margins obtained in greater than 80% of the patients. Newer trials are attempting to standardize the definition of borderline resectable pancreatic cancer and treatment regimens. In this review, we outline the definition, imaging requirements and management of patients with borderline resectable pancreatic cancer.     

Lung cancer: is there a place for elective nodal irradiation?]

The use of conformal radiotherapy in lung cancer has considerably evolved with the advent of improved staging technologies and methods of radiation delivery. Patients with limited disease, inoperable for medical reasons, may be treated with conformal radiotherapy alone; patients with more advanced disease are treated with combined chemo-radiotherapy. If local control may be improved by radiotherapy dose escalation according to several studies, toxicity and more particularly pulmonary toxicity seems to be related to radiation volume. Thus the use of elective nodal irradiation is being questioned. Data for early stage (stage I) non-small-cell lung cancer treated with conformal radiotherapy or stereotactic hypofractionated radiotherapy strongly supports the use of smaller fields that do not incorporate elective nodal regions; local control and survival rates approach those of surgical series. In locally advanced non-small cell lung cancer, eliminating elective nodal irradiation allows to maximize tumor dose and minimize normal tissue toxicity in combined modality treatments; results are encouraging. The use of staging modalities such as positron emission tomography and eventually oesophageal ultrasonography is increasing, allowing to encompass the tumor volume with more accuracy. Several studies have confirmed that involved-field irradiation results into a regional nodal rate of less than 10%. Further larger-scale studies would be needed to definitely establish "no elective nodal irradiation" as a standard in non-small cell lung cancer. There are very few data concerning small cell lung cancer.     

Preoperative chemoradiation and IOERT for unresectable or borderline resectable pancreas cancer

Background and objectives

Pre-operative chemoradiation (preop CRT) plus intraoperative electron irradiation (IOERT) has been used in the multidisciplinary treatment for patients with locally advanced unresectable or borderline resectable pancreas cancer. This review was performed to evaluate survival, relapse patterns and prognostic factors in patients treated with curative intent.

Methods

Between January 2002 and December 2010, 48 patients with locally advanced pancreatic ductal adenocarcinoma received preop CRT prior to an attempt at resection and IOERT. 31/48 (65%) patients proceeded to curative-intent surgical resection. Resection status prior to preop CRT was locally unresectable (20 patients) and borderline resectable (11 patients). Preop CRT (45-50.4 Gy/25-28 Fx in 27/31) was delivered with concurrent 5FU or gemcitabine-based regimens. Subsequent gross total resection was achieved in 16 patients (R0, 11; R1, 5). IOERT was delivered in 28 patients (dose, 10-20 Gy). 16 patients also received adjuvant post-operative systemic chemotherapy. Outcomes evaluated include survival, local failure in the EBRT field (LF), central failure in the IOERT field (CF), and distant metastases.

Results

Resection status was predictive for survival and for patterns of relapse. For patients with at least a gross total resection after preop CRT (R0/R1; n=16) vs. no resection (n=15), both median and overall survival were improved (median 23 vs. 10 months; 2-year, 40% vs. 17%; 3-year, 40% vs. 0%; P=0.002). Liver or peritoneal relapse was documented in 22/31 patients (71%); LF/CF in 5/26 (16%).

Conclusions

Long term survival and disease control are achievable in select patients with borderline resectable or locally unresectable pancreas cancer when gross total surgical resection is achieved after preop CRT. Continued evaluation of curative-intent combined modality therapy is warranted in this high risk population, but additional strategies are needed to improve resectability and disease control.Key Words: Pancreatic neoplasms, radiotherapy, chemotherapy, surgery, intraoperative procedures     

Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas

To determine the maximum tolerated dose and dose-limiting toxicity associated with twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas.

Twenty-one patients with biopsy-proven adenocarcinoma of the pancreas were treated with external-beam radiotherapy to a dose of 50.4 Gy in 28 fractions, concurrent with gemcitabine, infused over 30 min before irradiation on a Monday and Thursday schedule. The dose of gemcitabine was escalated in 5 cohorts of 3–6 patients each. Initial gemcitabine dose was 10 mg/m², with dose escalation until dose-limiting toxicity was observed.

The maximum tolerated dose of gemcitabine was 50 mg/m², when given in a twice-weekly schedule with radiation. Dose-limiting toxicity was seen in 2 patients at 60 mg/m², and consisted of severe upper gastrointestinal bleeding approximately 1 month after completion of treatment. Six patients had radiographic evidence of response to treatment, and 5 of these underwent complete surgical resection. Three patients who underwent complete resection had been deemed to have unresectable tumors before enrollment on trial. Four patients are alive, including 2 without evidence of disease more than 1 year after resection.

The combination of external-beam radiation and twice-weekly gemcitabine at a dose of 50 mg/m² is well tolerated and shows promising activity for the treatment of pancreatic cancer. Our data suggest a higher maximum tolerated dose and different dose-limiting toxicity than previously reported. Further investigation of this regimen is warranted.     

Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis

Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor.     

High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer

In the era of total mesorectal surgery, the issue of radiation toxicity is raised. A novel endocavitary brachytherapy technique was tested as a neoadjuvant treatment for patients with resectable rectal cancer. The objectives of the study were to evaluate the treatment-related toxicity and effects on local recurrence. A dose of 26 Gy was prescribed to the gross tumour volume and intramesorectal deposits seen on magnetic resonance imaging and given over four daily treatments, using the high dose rate delivery system followed by surgery 6-8 weeks later. The study included 93 T3, four T4 and three T2 tumours. Acute proctitis of grade 2 was observed in all patients, but one required transfusion. At a median follow-up time of 60 months, the 5-year actual local recurrence rate was 5%, disease-free survival was 65%, and overall survival was 70%. High dose rate endorectal brachytherapy seems to prevent local recurrence and has a favourable toxicity pattern compared with external beam radiotherapy.     

Treatment strategy for marginally resectable gastric cancer

It has been postulated that preoperative chemotherapy might promote tumor regression, eradicate nodal metastases, and improve resectability in patients with marginally resectable gastric cancer.For a marginally resectable tumor of gastric cancer, we selected the advanced gastric cancer patients with metastases and recurrences to the abdominal para-aortic lymph node (PAN), liver and invasion to the pancreas head and/or the duodenum.Patients with positive peritoneal cytology(P0, CY1)or localized peritoneal metastasis(P1), and Stage IV gastric cancer patients, were also considered candidates in this category. The strategy and results of surgical treatment for marginally resectable gastric cancer were explained as the dissection of PAN, hepatic resection, pancreaticoduodenectomy, perioperative chemotherapy for P0CY1 or P1, and neoadjuvant chemotherapy for Stage IV gastric cancer, which was still considered an experimental approach, although its use may be justified in unresectable or marginally resectable GC.The result of the resection of a marginally resectable gastric cancer is poor, but when there are no other non-curative factors, extended surgical resection should be performed because complete response is difficult at present with chemotherapy alone.In conclusion, there was no evidence suggesting that extended surgical procedures are effective, but a strategy of multidisciplinary treatment including extended surgical approach should be verified based on randomized controlled trials.     

A phase I study of combined UFT plus leucovorin and radiotherapy for pancreatic cancer

PURPOSE: This Phase I study combines tegafur and uracil (UFT) with leucovorin and conventional radiation for the treatment of pancreatic cancer. The design seeks to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of this regimen as well as to define a future Phase II dose level. METHODS: Patients with locally advanced and unresectable pancreatic cancer were treated with 45 Gy of radiation therapy. The initial UFT dose was 150 mg/m(2)/day given with leucovorin 90 mg/day, both divided into 3 daily doses for 35 days concurrent with radiation. UFT doses were escalated at increments of 50 mg/m(2)/day. Dose-limiting toxicity (DLT) was defined as Grade 3 or greater nausea, vomiting or diarrhea despite medical intervention; or Grade 3 or greater neutropenia/thrombocytopenia; or Grade 3 or greater hepatic toxicity; or inability of the patient to take 75% or more of the planned UFT/leucovorin; or radiotherapy interruption of greater than 1 week. The MTD for UFT/leucovorin was exceeded by one dose level when a certain dose caused DLT in 2 or more patients of 6. RESULTS: Five evaluable patients had Stage I resectable disease but had pathologic adenopathy. Seven had Stage II unresectable disease. Compliance with therapy was excellent. At a daily dose of 300 mg/m(2) of UFT, we noticed minimal diarrhea and hematologic toxicity with mild-moderate nausea, anorexia, and fatigue. Three patients had Grade 4 toxicity: 1 had neutropenia on Day 38, 1 had diarrhea on Day 55, and 1 had vomiting on Day 15. CONCLUSION: Oral UFT/leucovorin and radiation therapy offers patients a viable treatment option for pancreatic cancer. The major known toxicity of diarrhea was tolerable. The MTD was not reached in this study. Our current plan is to expand this into a Phase I/II trial beginning at a UFT dose of 300 mg/m(2) and correlate this with clinical pharmacologic parameters. The potential benefit of long bioavailability and oral delivery of UFT compares favorably with continuous infusion regimens without the added morbidity of a catheter and pump.     

Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer

PURPOSE: Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer. METHODS: Chemotherapy consisted of i.v. cisplatin 80 mg/m(2) (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m(2) increments, starting at 200 mg/m(2)/d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy. RESULTS: Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m(2)/d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery. CONCLUSION: The recommended UFT dose for Phase II studies is 200 mg/m(2)/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy.     

Proton therapy for pancreatic cancer

Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy.     

Comparative Dosimetric Analysis and Normal Tissue Complication Probability Modelling of Four-Dimensional Computed Tomography Planning Scans Within the UK NeoSCOPE Trial

AimsNeoSCOPE is a trial of two different neoadjuvant chemoradiotherapy regimens for resectable oesophageal cancer and was the first multicentre trial in the UK to incorporate four-dimensional computed tomography (4D-CT) into radiotherapy planning. Despite 4D-CT being increasingly accepted as a standard of care for lower third and junctional oesophageal tumours, there is limited evidence of its benefit over standard three-dimensional computed tomography (3D-CT).MaterialsUsing NeoSCOPE 4D-CT cases, we undertook a dosimetric comparison study of 3D-CT versus 4D-CT plans comparing target volume coverage and dose to organs at risk. We used established normal tissue complication probability models to evaluate the potential toxicity reduction of using 4D-CT plans in oesophageal cancer.Results4D-CT resulted in a smaller median absolute PTV volume and lower dose levels for all reported constraints with comparable target volume coverage. NTCP modelling suggests a significant relative risk reduction of cardiac and pulmonary toxicity endpoints with 4D-CT.ConclusionOur work shows that incorporating 4D-CT into treatment planning may significantly reduce the toxicity burden from this treatment.     

Electron intraoperative treatment in patients with early-stage breast cancer: data update

Intraoperative radiotherapy is a technique where a high, single-fraction radiation dose is delivered directly to the tumor bed during a surgical procedure, after the removal of a neoplastic mass, with minimal exposure of surroundings tissues, which are displaced and shielded during the procedure. Intraoperative radiotherapy has been used in the treatment of various malignancies, mostly in combination with external beam radiation therapy. The long-term results suggest a positive impact on local controls that appear to be associated with increased survival. Modern intraoperative radiotherapy can be performed either with electron beams or photons, and has been used recently in early-stage cancer as a boost or as an exclusive treatment, especially for breast tumors, with extremely promising results. The results of different clinical studies have demonstrated the feasibility of the technique and it is expected that its application will become more widespread in the immediate future. Intraoperative electron radiotherapy in the treatment of initial-stage breast cancer may be an excellent alternative to external beam radiation therapy in an appropriate selected group of patients. However, intensive long-term follow-up is required for a better evaluation of local control and possible side effects.     

Phase I trial of oxaliplatin in combination with cisplatin, protacted-infusion fluorouracil, and radiotherapy in advanced esophageal and gastroesophageal carcinoma

PURPOSE: To define the maximum-tolerated dose of oxaliplatin given with cisplatin, protacted 96-h infusion of fluorouracil, and radiotherapy for patients with advanced esophageal cancer. PATIENTS AND METHODS: Seventeen patients with locally advanced esophageal cancer and 2 patients with local recurrence were treated. Escalating doses of oxaliplatin, cisplatin, and fluorouracil were administered on Days 1 and 29 of radiotherapy. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy. Dose-limiting toxicity was defined as a Grade 4 hematologic or Grade 3-4 nonhematologic toxicity. RESULTS: Dose-limiting toxicity caused by diarrhea and asthenia was observed at the IV level. The recommended dose was 85 mg/m- oxaliplatin, 55 mg/m2 cisplatin, and 3000 mg/m2 96-h fluorouracil infusion. Two pathologic complete responses were observed in 12 patients selected for surgery (16%). CONCLUSIONS: Oxaliplatin, cisplatin, fluouracil, and radiotherapy can be administered together with acceptable toxicity. A Phase II trial is ongoing with resectable esophageal and gastric carcinoma.     

Treatment of cancer of the pancreas by intraoperative electron beam therapy: physical and biological aspects

Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means of verification. Emphasis is placed on the collaboration and cooperation necessary for all members of the intraoperative radiation therapy team including surgeons, radiation therapists, medical physicists, anesthesiologists, technologists, and nurses.     

Gastro-intestinal and genito-urinary morbidity after 3D conformal radiotherapy of prostate cancer: observations of a randomized trial.

BACKGROUND AND PURPOSE: The late morbidity of a randomized study was analyzed after a follow up of 2 years. The difference in intestinal morbidity was analyzed as a function of the treatment arm and dose volume parameters. The correlation with acute toxicity and (pre-existing) bowel complaints was investigated. PATIENTS AND METHODS: 266 T1-4N0M0 prostate cancer patients were randomized for conventional (open fields) and 3D conformal radiotherapy using beams eye view blocked fields with the same dose (66 Gy) and gross target volume-planning target volume margin (15 mm). Apart from the RTOG toxicity scoring system a patient self-assessment questionnaire was used to obtain detailed information on morbidity. RESULTS: At 2 years there is only a trend for less rectal toxicity (grade >/=1) in favor of the conformal radiotherapy (grade 1, 47 versus 40% and grade 2, 10 versus 7% for conventional and conformal radiotherapy, respectively (P=0.1). A significant relation was found between late rectal toxicity (grade >/=1) and the volume of the anus and rectum exposed to >/=90% tumor dose (TD). A highly significant relationship is observed between acute rectum and anal toxicity and late rectal toxicity. The patient self-assessment questionnaire analysis revealed that patients are most bothered by compliance related symptoms like urgency, soiling and fecal loss. In a multivariate analysis, all other variables loose significance, when anal volume exposed to >/=90% TD and pre-treatment defaecation frequency are accounted for. Late anal toxicity is low and related only to acute anal toxicity. Late bladder toxicity is related solely to pre-treatment frequency and overall urological symptoms. The incidence of grade 2 toxicity increases with a factor 2.5-4 when (stool or urine) frequency is unfavorable at the start of treatment. CONCLUSIONS: Conformal radiotherapy at the dose level of 66 Gy does not significantly decrease the incidence of rectal, anal and bladder toxicity compared to conventional radiotherapy. There is a significant relationship between acute and late toxicity and the anal volume exposed to 90% TD. Intestinal (and urological) symptoms at start have a major impact on late toxicity.     

Precision radiotherapy for cancer of the pancreas: technique and results

Forty patients with locally extensive, unresectable adenocarcinoma of the pancreas received precision high dose (PHD) radiation therapy with a 45 MeV betatron. A histologic diagnosis of cancer was established at laparotomy in every case. The gross margins of the tumor were outlined with radio-opaque clips in all but one case. The clipped tumor volume plus a 1 to 3 cm margin was irradiated to a minimum dose of 5900 to 7000 rad in 180 rad fractions over 7 to 9 weeks. For slender patients, a “mixed beam” technique was employed: opposed lateral 45-MeV photon beams mated to an anterior “mixed beam” consisting of 50 % 45-MeV photons and 50% 15–35 MeV electrons. The choice of electron energy depended upon the depth of the posterior margin of the target volume. For non-slender patients, a “box” technique consisting of 3 or 4 fields of 45-MeV photons was used. Where indicated, fields were shaped to conform the isodose distribution to the shape of the target volume. PHD radiotherapy was generally well tolerated. During !treatment, only 7 patients experienced significant nausea, vomiting, diarrhea or anorexia. Late gastrointestinal radiation reactions were observed in 7 patients (severe in 3 patients). Twelve patients received adjuvant chemotherapy. Relief of pain occurred in $\text{22}\text{32}$ patients and anorexia improved in $\text{8}\text{15}$ patients following PHD radiotherapy. The projected survival of patients with unresectable pancreatic cancer treated with PHD radiotherapy is comparable to that of patients with resectable disease operated on for cure. The projected one year survival rate is 49%.     

术中放疗在术中不可切除T4期胰腺癌的应用研究

[目的]对术中不可切除T4期胰腺癌进行单纯术中电子线放疗研究,探讨其安全性和疗效。[方法]2009年12月～2011年7月共入组16例术中不可切除的T4期胰腺癌。术中行电子线放疗,中位剂量18Gy,术后依病情决定是否给予化疗。分析手术时间、住院时间、不良反应、局部控制以及生存情况。[结果]手术中位时间180min,术后住院中位时间10.5d,未观察到3度以上的不良反应。1年局部控制率80.0%,1年生存率12.5%,中位生存期9.5个月。[结论]对术中不可切除的T4病变进行单次16～20Gy以上的术中放疗有效且耐受性好,能达到术后同步放化疗相似的生存率及局部控制率。但整体远处转移率高,建议对能耐受者应给予化疗。