Biomedical subjects

Kaled M Alektiar

Publications and source records attributed to Kaled M Alektiar.

At least 19 recordsLinked to original sources

PubMed2007

Twelve-year experience in the management of endometrial cancer: a change in surgical and postoperative radiation approaches.

OBJECTIVE: Over the past 12 years, the primary management of endometrial cancer at a comprehensive cancer center has undergone changes characterized by the increased use of laparoscopic surgery with comprehensive staging resulting in a decreased reliance on postoperative adjuvant whole pelvic radiation therapy (WPRT). The purpose of this study was to analyze the results of these changes. MATERIALS AND METHODS: Between 1/93 and 12/04, 1312 patients underwent surgery for endometrial cancer consisting of either abdominal or laparoscopic hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO or LAVH/BSO). Pelvic and para-aortic lymph node dissection was performed at the discretion of the attending physician. Postoperative adjuvant treatment employed in patients with high-risk features consisted mainly of WPRT+/-intravaginal radiation therapy (IVRT). Total direct medical charges incurred from 10 days prior to surgery through 75 days after surgery were determined with charges converted to direct medical costs, taking into account inflationary changes. RESULTS: The median age at diagnosis for all patients was 62 years (range, 21-93 years), with a median follow-up of 31.6 months (range, 0-140 months). There was a significant increase in LAVH/BSO versus TAH/BSO (P<0.001) until 2001 when we began participating in a national randomized trial of laparoscopic versus abdominal surgery. In addition, there was a significant increase in the percentage of patients undergoing lymph node dissection as well as the median number of nodes removed (P<0.001). This was associated with a significant decrease in the use of WPRT during 1993-1998 versus 1999-2004 (P<0.001). The use of IVRT remained the same during these time periods. There was no significant difference in 1-, 2-, or 5-year survival for patients treated in either time period. Cost data were available from 1995 to 2004. There was a significant increase in the median total direct medical costs when comparing periods 1995-1998 with 1999-2004 (P<0.001), although the median cost of pelvic radiation therapy was lower in the later time period. CONCLUSION: Over a 12-year period, the primary management of endometrial cancer changed to include an increased use of laparoscopy and comprehensive surgical staging and a decrease in the use of postoperative adjuvant WPRT, with no appreciable negative effect on overall survival.

Adult↗

PubMed2006

Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study.

PURPOSE: To determine overall survival and progression-free survival among patients with high-risk, stage III and IV endometrial cancer who receive paclitaxel and carboplatin (TC) after complete tumor resection. PATIENTS AND METHODS: Patients with stage III/IV endometrial cancer with less than 2 cm of disease after surgical resection who received TC in the adjuvant setting were retrospectively identified and are the subject of this analysis. Data were extracted from electronic medical records. Disease recurrence was documented by radiologic progression or pathologic tissue review. We obtained Institutional Review Board approval before initiating this study. RESULTS: Forty-eight patients were eligible for analysis--24 (50%) with stage IV disease, 29 (60%) with serous or clear cell tumor histology and 43 (90%) with FIGO grade 3 tumors. All patients underwent surgical resection; 10 (21%) of the 48 patients received adjuvant radiation therapy in addition to chemotherapy. Forty-three patients (90%) received 6 cycles of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve of 5-6) every 3 or 4 weeks, and 44 (92%) completed all planned cycles of treatment. With a median follow-up of 20 months (range, 6-92), 29 patients (60%) recurred, with a 3-year overall survival rate of 56%. The median time to progression for all patients was 13 months (95% CI 10, 18) with a median OS of 47 months (95% CI, 30--upper limit not achieved). CONCLUSION: TC is a well tolerated, active regimen in the treatment of resected, high-risk stage III and IV endometrial cancer that warrants further investigation.

Adult↗

PubMed2006

Surgical resection of recurrent endometrial carcinoma.

OBJECTIVE: Chances of survival after the diagnosis of recurrent endometrial cancer are poor. Although total pelvic exenteration has been described as a treatment for a select subset of patients with recurrent endometrial cancer, the use of other surgical procedures in this setting has not been well described. The objective of this study was to review our experience with non-exenterative surgery for recurrent endometrial cancer. METHODS: We reviewed the medical records of all patients who underwent non-exenterative surgery for recurrent endometrial cancer between 1/91 and 1/03. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. RESULTS: Twenty-seven patients were identified. Fifteen patients (56%) had disease limited to the retroperitoneum, 10 patients (37%) had intraperitoneal disease, and 2 patients (7%) had both intra- and retroperitoneal disease. Cytoreduction to 2 cm. There were no major perioperative complications or mortalities. The median hospital stay was 7 days (range, 1-18 days). Additional therapies included intraoperative radiation therapy in 9 patients (33%), radiation therapy in 12 patients (44%), and chemotherapy in 10 patients (37%). The median follow-up for the entire cohort was 24 months (range, 5-84 months). The median progression-free survival was 14 months (95% CI, 6-23), and the median disease-specific survival was 35 months (95% CI, 24-not reached). Size of residual disease was the only significant predictor for both progression-free and disease-specific survival. Patients with residual disease 2 cm residual (P = 0.01). CONCLUSIONS: Surgical resection for recurrent endometrial cancer may provide an opportunity for long-term survival in a select patient population. The only factor associated with improved long-term outcome was the size of residual disease remaining at the end of surgical resection.

Aged↗

PubMed2006

When and how should adjuvant radiation be used in early endometrial cancer?

The role of adjuvant radiation therapy (RT) in early endometrial cancer is no longer clearly defined. The increased use of surgical lymph nodes staging and the perceived "lack of survival advantage" with adjuvant pelvic RT leads to a wide array of conclusions on who should be treated and if so how. The purpose of this review is 2-fold: first, to determine the scientific validity of some of the conclusions drawn about the lack of survival impact of adjuvant pelvic RT and, second, to determine which treatment option provides the best therapeutic ratio. Overall survival may not be the ideal endpoint for early-stage endometrial cancer where death more often than not is because of causes other than endometrial cancer. Observation after hysterectomy may have the best morbidity profile, yet it may not be the option with the best therapeutic ratio. Finding a suitable alternative such as intravaginal RT or using intensity-modulated radiation therapy may ultimately prove to be the option with the best therapeutic ratio. The data learned from surgical lymph nodes staging and from the 2 recent randomized trials on the role of pelvic RT in early endometrial cancer need not be ignored nor held as the final answer. Perhaps, rectal cancer should be used as an example of how an incremental use of individual adjuvant therapies, each impacting outcome little at a time, ended up improving overall survival. If we were to use the current prevailing approach in endometrial cancer for rectal cancer, patients would still be treated with surgery alone.

Adenocarcinoma↗

PubMed2005

Mesorectal lymph node involvement and prognostic implications at total pelvic exenteration for gynecologic malignancies.

OBJECTIVES: To determine the incidence and prognostic implications of positive mesorectal lymph nodes in patients undergoing total pelvic exenteration for recurrent gynecologic malignancies. METHODS: We performed a retrospective chart review of all patients who had undergone total pelvic exenteration for a gynecologic malignancy between July 1992 and December 2003. Patient charts were reviewed for information regarding demographics, site of cancer, histology, pathology report, and time to recurrence. RESULTS: Fifty-eight women had undergone total pelvic exenteration for recurrent gynecologic malignancies during the study period and 57 were available for analysis. Primary cancer site was as follows: cervix, 37 (65%); vagina, 8 (14%); vulva, 5 (9%); and uterine corpus, 7 (12%). In 30 patients (53%), the mesorectal lymph node status was pathologically evaluated. Of these 30 patients, 3 (10%) had positive mesorectal lymph nodes at the time of total pelvic exenteration. All 3 patients had rectal wall involvement (rectal submucosa, 2; rectal mucosa, 1), and all 3 patients recurred within 4 months of pelvic exenteration. The median time to recurrence after surgery was 2.4 months in those patients with positive mesorectal lymph nodes compared with 7.3 months in those with negative mesorectal lymph nodes (P = 0.005). When individually adjusted for other prognostic variables, such as margin status, tumor grade, lymphovascular space involvement, primary cancer site, and histologic type, a finding of positive mesorectal lymph nodes was associated with a shorter time to recurrence of disease (all P < 0.05). CONCLUSIONS: Mesorectal lymph node involvement is a common finding at total pelvic exenteration, particularly in patients with rectal wall involvement. Patients with positive mesorectal lymph nodes appear to have a worse outcome with a shorter time to recurrence of disease.

Adolescent↗

PubMed2005

Radiation therapy for Ewing's sarcoma: results from Memorial Sloan-Kettering in the modern era.

PURPOSE: To evaluate the outcomes of patients with Ewing's sarcoma family of tumors (ESFT) treated with modern radiotherapy techniques with MRI along with optimal chemotherapy. METHODS AND MATERIALS: The records of all 60 patients with ESFT who received radiation to the primary site between 1990 and 2004 were reviewed. All patients received chemotherapy, including vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. Radiation was used as the sole modality for local control in 31 patients and was given either before (n=3) or after surgical resection (n=26) in the remainder. All patients had MRI and CT scan-based treatment planning, and 43% received intensity-modulated radiation therapy. Radiation doses ranged from 30 Gy to 60 Gy (median, 51 Gy), and 35% received hyperfractionated radiotherapy. RESULTS: Median age was 16 years (range, 2-40 years). Because of selection bias for radiotherapy, the majority of primary tumors were centrally located (72%): spine (n=18), pelvis (n=15), extremities (n=12), chest wall (n=5), head and neck (n=5), and other (n=5). Thirty-eight percent of patients presented with metastatic disease, and 52% of primary tumors were >or=8 cm. Actuarial 3-year local control was 77%. The presence of metastases at diagnosis was an adverse prognostic factor for local control (84% vs. 61%, p=0.036). No other predictive factors for local failure were identified. In patients without metastatic disease, 3-year disease-free and overall survival rates were 70% and 86%, respectively, whereas in patients with metastases they were both 21%. Follow-up of surviving patients was 6-178 months (median, 41 months). CONCLUSION: In this unfavorable cohort of ESFT patients, radiation therapy was an effective modality for local control, especially for patients without metastases. The presence of metastases at diagnosis is a predictive factor not only for death but also for local failure.

Adolescent↗

PubMed2005

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity.

PURPOSE: The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. METHODS AND MATERIALS: Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and 45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. RESULTS: The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more received a conventional radiation dose (p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77-86%), 61% (95% CI, 56-66%), and 71% (95% CI, 66-76%), respectively. The 5-year local control rate in patients with UE STS was 70% (95% CI, 60-80%) compared with 86% (95% CI, 81-91%) for LE STS (p = 0.0004). On multivariate analysis, an UE site (p = 0.001; relative risk [RR], 3; 95% CI, 2-5) and positive resection margins (p = 0.02; RR, 2; 95% CI, 1-4) were significant predictors of poor local control. The RT type or radiation dose, age, tumor depth, and size were not significant predictors of local control. The 5-year wound reoperation rate was 1% (95% CI, 0-3) in the UE compared with 11% (95% CI, 7-15) in the LE (p = 0.002). On multivariate analysis, the UE site retained its significance as a predictor of low wound complications (p = 0.001; RR, 0.08; 95% CI, 0.01-0.7). The site did not significantly influence the incidence of fracture (p = 0.7), joint stiffness (p = 0.2), edema (p = 0.5), or Grade 3 or worse peripheral nerve damage (p = 0.3). CONCLUSION: The UE site is associated with a greater rate of local recurrence compared with the LE. This difference was independent of other variables and could not be accounted for by an imbalance between the two groups. With a lower wound complication rate associated with an UE site, it would be of interest to determine whether preoperative RT and/or intensity-modulated RT can increase the local control in UE sarcomas, thus improving the therapeutic ratio.

Adolescent↗

PubMed2005

Intravaginal brachytherapy alone for intermediate-risk endometrial cancer.

PURPOSE: Despite the results of the Gynecologic Oncology Group trial No. 99 (GOG#99), some unanswered questions still remain about the role of adjuvant radiotherapy (RT) for intermediate-risk endometrial cancer. First, can intravaginal brachytherapy (IVRT) alone substitute for external beam RT but without added morbidity? Second, is the high-risk (HR) definition from GOG#99 a useful tool to predict pelvic recurrence specifically? The purpose of this study was to try to answer these questions in a group of patients with Stage IB-IIB endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. METHODS AND MATERIALS: Between November 1987 and December 2002, 382 patients with Stage IB-IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR-IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20% of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy (range, 6-21 Gy), given in three fractions. Complications were assessed in terms of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI tract, genitourinary GU tract, and vagina. RESULTS: With a median follow-up of 48 months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate correlated with age > or =60 years old (relative risk [RR], 3, 95% CI, 1-12; p = 0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR, 9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth of myometrial invasion and CSS, however, were not significant. With regard to pelvic control specifically, the presence of GOG#99 HR features did not affect the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90-100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when the CSS effect was taken into account, the influence of HR features on pelvic control was still not significant (p = 0.51). In contrast, pelvic control was significantly influenced when patients were grouped according to CSS and stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93% (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated with age > or =60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95% CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p = 0.054). Unlike pelvic control, disease-free survival was significantly affected by GOG#99 HR features, with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those without HR features (p = 0.027). The 5-year overall and disease-specific survival rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3 or worse complications was 1% (95% CI, 0-2%). CONCLUSION: Tumor grade, depth of invasion, and the use of CSS were better predictors of pelvic control than the GOG#99 HR factors. IVRT alone seemed to provide adequate tumor control with very low morbidity. Therefore, it seems prudent to consider it for intermediate-risk patients because of its superior therapeutic ratio compared with that for surgery alone or pelvic RT. Additional follow-up, however, with a larger number of patients is needed, especially for those with LVI.

Aged↗

PubMed2005

Prognostic factors for survival in patients with locally recurrent extremity soft tissue sarcomas.

BACKGROUND: Factors prognostic for survival in patients with locally recurrent extremity soft tissue sarcomas (STS) are poorly defined, thus making it difficult to identify high-risk patients who may benefit from adjuvant therapy. METHODS: A total of 1421 patients underwent surgical treatment for primary extremity STS at a single institution between 1982 and 2002. Of these, 179 (13%) patients underwent complete surgical resection of an isolated local recurrence and were the subjects of this study. Clinicopathologic factors from both the primary tumor and the local recurrence were analyzed. RESULTS: The median interval to initial local recurrence was 16 months: 65% developed a local recurrence by 2 years and 90% by 4 years. Only four patients who presented with a low-grade primary tumor progressed to a high-grade local recurrence. Independent prognostic factors for disease-specific survival after local recurrence were a high histological grade (hazard ratio, 5.1; P = .0004), a large local recurrence tumor size (hazard ratio, 1.5; P = .0001), and a short local recurrence-free interval (hazard ratio, 1.6; P = .0001). Patients who developed a local recurrence >5 cm in < or =16 months (n = 44; 0 low grade) had a 4-year disease-specific survival of 18%, compared with 81% for patients who developed a local recurrence < or =5 cm in >16 months (n = 46; 11 low grade). CONCLUSIONS: Histological grade, local recurrence size, and local recurrence-free interval are independently predictive of survival in patients with locally recurrent extremity STS. A large local recurrence that develops in a short interval indicates a biologically aggressive tumor with a high tumor-specific mortality. Patients who develop such recurrences are ideal subjects for systemic neoadjuvant therapy trials.

Adolescent↗

PubMed2004

Intensity-modulated radiotherapy for soft tissue sarcoma of the thigh.

PURPOSE: Fracture of the femur is one of the late complications of adjuvant radiotherapy for patients with soft tissue sarcomas of the thigh, who receive external beam irradiation after limb-sparing surgery. When the target volume approximates the femur, it is often inevitable that a large segment of the femur will receive full prescription dose with conventional radiation techniques. We report the dosimetric feasibility of intensity- modulated radiation therapy (IMRT) techniques to achieve adequate target coverage and bone sparing. METHODS AND MATERIALS: Treatment planning was performed using both three-dimensional conformal radiotherapy (3D-CRT) and IMRT techniques for 10 patients with soft tissue sarcoma of the thigh with tumor approaching the femur. None of the patients had bony involvement. For all patients, the gross total volume (GTV) and the femur were contoured. The clinical target volume (CTV) was defined as the GTV with a 1.5-cm margin axially, except at the bone interface where the bone interface was used as CTV if the 1.5-cm axial margin extended beyond the bone interface. In the superior-inferior direction, the CTV margin placed around the GTV varied from 5 to 10 cm. The planning target volume (PTV) was defined as the CTV with 5-mm margin all around. The 3D conformal technique consisted primarily of two to three beams with wedges or partial transmission blocks as compensators. For the IMRT technique, five coplanar beams were used, chosen so as to spare much of the surrounding soft tissue and to clear the other extremity or groin areas. IMRT plans were designed to adequately treat the planning target volume and spare the femur as much as possible. RESULTS: Dose distributions and dose-volume histograms were analyzed. PTV coverage was comparable with both IMRT and 3D-CRT plans. Dose distributions were more conformal with IMRT, however, especially for patients with large variations of contours. The volume of the femur receiving at least full prescription (63 Gy) V100 decreased on average by approximately 57%, from 44.7 +/- 16.8% with 3D-CRT to 18.6 +/- 9.2% with IMRT (p < 0.01). For 3 patients with a GTV surrounding <50% of the circumference of the femur, the reduction in the V100 to the femur ranged from 61% to 79%. The hot spots in the femur, as measured by D05 (the dose encompassing 5% of volume), reduced on average from 67.2 +/- 1.8 Gy with 3D-CRT to 65.0 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the femur was on average 38.5 +/- 11.5 Gy with IMRT, compared with 40.9 +/- 12.7 Gy with 3D-CRT. The volume of the surrounding soft tissues, defined as the ipsilateral limb excluding the PTV and the femur, receiving at least prescription dose (63 Gy) was reduced on average by about 78%, from 997 +/- 660 cc with 3D-CRT to 201 +/- 144 cc with IMRT (p < 0.01). The D05 to the surrounding soft tissues was on average 58.7 +/- 4.7 Gy with IMRT, compared to 67.8 +/- 1.3 Gy with 3D-CRT (p < 0.01), a reduction of approximately 13%. The mean dose to the surrounding soft tissues was comparable in both plans. The volume of the skin (from surface to 5 mm depth) receiving prescription dose (63 Gy) declined by roughly 45%, from 115 +/- 40 cc with 3D-CRT to 61 +/- 20 cc with IMRT (p < 0.01), with IMRT providing full skin dose coverage to scars. The hot spots in the skin decreased from 68.0 +/- 1.7 Gy with 3D-CRT to 65.2 +/- 1.2 Gy with IMRT (p < 0.01). The mean dose to the skin lessened from 51.5 +/- 4.7 Gy with 3D- CRT to 44.0 +/- 4.2 Gy with IMRT (p < 0.01), a reduction of 14%. CONCLUSIONS: Intensity-modulated radiation therapy techniques can reduce the dose to the femur without compromising target coverage by achieving concave dose distributions around the interface of the PTV and the femur. At the same time, IMRT can reduce the hot spots significantly in the surrounding soft tissues and skin. Whether such dosimetric improvements can translate into reduction of complications and/or improving local control needs to be investigated.

Femur↗

PubMed2004

Colorectal cancer pelvic recurrences: determinants of resectability.

PURPOSE: This study was designed to identify preoperative and intraoperative features of locally recurrent colorectal cancer that predict R0 resection in patients scheduled for attempted complete resection followed by intraoperative radiation therapy. METHODS: Review of a prospective data base identified 119 patients brought to the intraoperative radiation therapy suite for planned complete resection of locally recurrent rectal (n = 101) and colon (n = 18) cancer between January 1994 and November 2000. R0 resection was achieved in 61 patients. This group was compared with patients in which an R1 (n = 38), R2 (n = 7), or palliative procedure (n = 13) was performed. Variables evaluated included: tumor location, features of the primary tumor, and preoperative findings on computed tomography, magnetic resonance imaging, and history/physical. Tumor location was established by review of operative/pathologic reports and classified as axial (anastomotic/perineal), anterior (bladder/genitourinary organs), posterior (presacral), or lateral (pelvic sidewall). RESULTS: When recurrence was confined to the axial location only, or axial and anterior locations, R0 resection was achieved significantly more often than when other locations were involved (P < 0.001, P = 0.003, respectively). When a lateral component was present, R0 resection was achieved significantly less often than when there was no lateral component (P = 0.002). For patients with available preoperative computed tomography and/or magnetic resonance imaging results (n = 70), the finding of lateral tumor involvement was associated with R0 resection significantly less often than when lateral disease was not identified (P = 0.004). CONCLUSIONS: Pelvic recurrences confined to the axial location, or axial and anterior locations, are more likely to be completely resectable (R0) than those involving the pelvic sidewall. Efforts to enhance preoperative identification and imaging of these patients are clearly justified.

Adult↗

PubMed2004

Outcome of split-thickness skin grafts after external beam radiotherapy.

There are many technical considerations in patients who require radiotherapy after oncologic reconstruction. A traditional tenet is to avoid skin grafts in this setting. However, this is not always avoidable. Therefore, the objective of this study was to evaluate the wound healing and functional outcome of patients in the authors' institution whose skin grafts were subsequently irradiated. A retrospective analysis of all patients treated with split-thickness skin grafts and postoperative radiotherapy at Memorial Sloan-Kettering Cancer Center from 1995 to 2002 was performed. Parameters evaluated included indications for skin graft, defect size, time to postoperative radiotherapy, total radiotherapy dose, delays and interruptions in radiotherapy, wound complications, and the need for further skin grafting. There were 30 patients (23 men, 7 women) with a mean defect size of 152 +/- 132 cm2. All split-thickness skin grafts were placed on healthy vascular tissue beds. In most instances (67%) skin grafts were used to cover muscle flaps. Median time to initial radiotherapy after grafting was 8 weeks (range, 4-60 weeks). There was 1 delay and 4 interruptions in radiotherapy treatment. There were 2 partial skin graft losses (<20%) after radiation that healed with conservative treatment. There was 1 complete skin graft loss after radiotherapy that required regrafting. Split-thickness skin grafts can tolerate postoperative radiotherapy without significant complications. Postoperative external beam radiation can begin as early as 6 to 8 weeks after skin grafting. If the requirement for postoperative radiotherapy is known, split-thickness grafts should ideally be placed on well-vascularized muscle beds. Minor skin graft loss resulting from postoperative radiotherapy can usually be treated conservatively without the need for additional surgery.

Adolescent↗

PubMed2003

Is endometrial carcinoma intrinsically more aggressive in elderly patients?

BACKGROUND: The current study was conducted to determine the influence of old age (age >/= 70 years) on outcome in a group of patients with endometrial carcinoma who were treated with simple hysterectomy followed by adjuvant radiation therapy (RT). METHODS: Between November 1987 and May 2000, 405 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB-II endometrial carcinoma were treated with postoperative RT. Intravaginal RT alone was given to 77% of patients (median dose, 21grays [Gy] given in 3 fractions). Additional postoperative external beam radiation therapy (EBRT) was given to 23% of patients (median dose, 45 Gy). Eighty-four patients were age >/= 70 years and 321 patients were age < 70 years. The two groups were well balanced with regard to race, comprehensive surgical staging, aggressive histology, lymphovascular invasion, lower uterine segment involvement, cervical involvement, and the use of postoperative EBRT. Significantly more patients in the age >/= 70 years group had other comorbidities such as obesity, diabetes mellitus, or hypertension (P = 0.02) and were found to have deep (> 50%) myometrial invasion (P = 0.008). RESULTS: With a median follow-up time of 48 months, the 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were 95%, 91%, and 90% respectively. On multivariate analysis, poor LRC was found to be correlated with age >/= 70 years (P = 0.019) and lymphovascular invasion (P = 0.001). Poor DFS was found to be correlated with age >/= 70 years (P = 0.03), lymphovascular invasion (P = 0.01), and aggressive histology (P = 0.001). Similarly, poor OS was found to correlate with age >/= 70 years (P = 0.001), lymphovascular invasion (P = 0.01), aggressive histology (P = 0.01), and cervical involvement (P = 0.02). The same factors that were found to correlate with OS (age >/= 70 years, lymphovascular involvement, aggressive histology, and cervical involvement) also appeared to correlate with disease-specific survival (P = 0.03, P = 0.008, P = 0.001, and P = 0.04, respectively). The 5-year actuarial rates of Radiation Therapy Oncology Group late complications that were >/= Grade 3 (gastrointestinal tract, genitourinary tract, or vagina) were 3% in both groups. CONCLUSIONS: Even when treated in a similar fashion, endometrial carcinoma patients age >/= 70 years appear to fare worse than younger patients independent of other poor prognostic factors. The rate of complications from adjuvant RT, despite a higher rate of comorbidity in elderly patients, was found to be similar in both age groups. Endometrial carcinoma appears to be intrinsically more aggressive in older patients, thus mandating further improvement in their treatment strategies.

Adult↗

PubMed2003

Tolerance of tissue transfers to adjuvant radiation therapy in primary soft tissue sarcoma of the extremity.

PURPOSE: Treatment of extremity sarcomas occasionally requires tissue transfer in the form of pedicle flaps, free flaps, or skin grafts to repair surgical defects. These tissues are often subject to radiation (RT) and are therefore at risk for wound breakdown requiring reoperation. This study reviews a single center's experience with tissue transfer and postoperative RT. METODS AND MATERIALS: Between 1983 and 2000, 43 adult patients (>16 years old) with primary high-grade soft tissue extremity sarcomas underwent limb-sparing surgery and reconstruction of their surgical defects, followed by adjuvant RT. The reconstructions were as follows: pedicle flaps (n = 14), free flaps (n = 10), skin grafts (n = 4), or a combination (n = 15). Postoperative external beam radiation therapy (EBRT) (median dose: 63 Gy) alone was given to 27 patients (63%). Adjuvant brachytherapy (BRT) was given to 16 patients (37%); BRT alone (median dose: 45 Gy) was given to 12 patients and combined with EBRT for 4 patients (EBRT: 45 Gy; BRT: 20 Gy). Comorbid conditions such as diabetes, hypertension, tobacco use, and obesity (calculated using body mass index >or=30) were present in 30 patients (70%). Tumor characteristics were as follows: 26 were >5 cm in size, 37 were deep, and 30 were in the lower extremity. The median follow-up time, calculated from the date of operation, was 32 months. Five of 43 patients suffered wound complications necessitating reoperation; however, 3 patients developed complications before initiation of RT and were therefore excluded from the analysis. Two of 43 patients (5%) required reoperation for wound complications after RT; 1 of these patients ultimately required amputation for necrosis. The 5-year overall wound reoperation rate was 6% (95% confidence interval: 0-14%). The influence of patient and tumor characteristics, as well as the type of RT, on the wound reoperation rates is as follows: BRT vs. EBRT (17% vs. 0%, p = 0.06); upper vs. lower extremity (0% vs. 8%, p = 0.41); 5 cm (8% vs. 4%, p = 0.9); comorbidity vs. no comorbidity (3% vs. 13%, p = 0.8); age 50 (8% vs. 4%, p = 0.8). CONCLUSION: Based on this review, most tissue transfers (95%) tolerated subsequent adjuvant radiation therapy well. Although more wound complications necessitating reoperation were seen in patients who received BRT, whether this is because of the inherent susceptibility of flaps and skin grafts to breakdown in the immediate postoperative period vs. the direct result of BRT needs further investigation.

Adolescent↗

PubMed2002

Outcome of primary soft tissue sarcoma of the knee and elbow.

PURPOSE: Concern is frequently raised regarding the tolerance of irradiation over a joint space. The purpose of this study was to determine the outcome in terms of relapse and potential complications in patients with knee and elbow soft tissue sarcoma treated with limb-sparing surgery with or without adjuvant radiotherapy (RT). METHODS AND MATERIALS: A review of our prospective database between June 1982 and December 1999 identified 86 adult patients with primary soft tissue sarcoma arising from the knee (n = 65; 76%) or elbow (n = 21; 24%) treated with limb-sparing surgery. Tumors had high-grade histologic features in 72% and were >5 cm in 48% of patients. Adjuvant RT was given to 46 (54%) of 86 patients. The type of RT was postoperative external beam RT in 63% and brachytherapy in 37%. Of the 46 patients who received RT, 85% (n = 39) had deep, 78% (n = 36) high-grade, and 54% (n = 25) >5-cm tumors. Complications were assessed in terms of wound complications requiring repeated surgery, bone fracture, nerve damage, and joint stiffness. RESULTS: With a median follow-up of 48 months (range 4-175), the 5-year actuarial rate of local control, distant control, and overall survival was 75% (95% confidence interval [CI] 64-85%), 82% (95% CI 73-91%), and 81% (95% CI 71-91%), respectively. The 5-year local control rate for patients who received RT was 80% vs. 71% for those who did not (p = 0.3). The type of RT did not significantly influence the local control rate. Patients treated with external beam RT had a 5-year local control rate of 84% compared with 73% for those treated with brachytherapy (p = 0.4). On multivariate analysis, tumor size >5 cm retained its significance as an independent predictor of poor local control (p = 0.04; relative risk 3; 95% CI 1-6). In addition, high-grade histologic features emerged as an independent predictor of local recurrence (p = 0.02; relative risk 4; 95% CI 1-20). No statistically significant difference was found between the RT and no-RT group in terms of the 5-year actuarial rate of wound reoperation (10% vs. 3%, p = 0.1), bone fracture (3% vs. 5%, p = 0.5), or nerve damage (6% vs. 3%, p = 0.5). Joint stiffness was significantly higher in the RT group (24% vs. 0%, p = 0.001), but this stiffness was severe to moderate in only 2 patients. CONCLUSION: On the basis of the findings of this retrospective review, adjuvant RT seems to be relatively well tolerated despite the inclusion of part of the joint space in the irradiation portal. Joint stiffness was seen more frequently with adjuvant RT, but it was moderate to severe in only a small number of patients.

Adolescent↗

PubMed2002

Is there a difference in outcome between stage I-II endometrial cancer of papillary serous/clear cell and endometrioid FIGO Grade 3 cancer?

PURPOSE: Several reports in the literature have shown that, compared with endometrioid adenocarcinoma, patients with papillary serous (PS) and clear cell (CC) histologic features do worse. However, it is unclear whether the outcome of PS/CC cancer is different from that of poorly differentiated endometrioid cancer. The purpose of this study was to compare the outcome between PS/CC and endometrioid International Federation of Gynecology and Obstetrics (FIGO) Grade 3 cancer and was limited to patients with Stage I-II uterine carcinoma. METHODS AND MATERIALS: Between November 1987 and September 1999, 83 patients with Stage I endometrial cancer and Stage II occult endometrial cancer were treated with simple hysterectomy and high-dose-rate intravaginal brachytherapy. Forty-one patients (49%) had FIGO Grade 3 endometrioid tumors (Group 1) and 42 (51%) had PS/CC histologic features (Group 2). The mean age was 63 years (range 30-89). Comprehensive surgical staging was done in 23 (28%) of 83 patients. Capillary space-like invasion (CSLI) was seen in 24 (29%) of 83 patients. The median dose of intravaginal brachytherapy when used alone was 21 Gy in 3 fractions. Additional external beam radiotherapy was given to 42 (51%) of 83 patients to 45 Gy. The two groups were balanced with regard to age, race, comprehensive surgical staging, amount of myometrial involvement, CSLI, lower uterine segment involvement, cervical involvement, and use of external beam radiotherapy. The median follow-up was 46 months (range 4-147). RESULTS: The pattern of relapse was as follows: vagina/pelvis in 5 of 14 patients, lungs in 8 of 15, intra-abdominal in 4 of 12, and supraclavicular lymph nodes in 1 of 14. One of the four intra-abdominal disseminations was in Group 1 and the other three in Group 2 (p = 0.6). The 5-year vaginal/pelvic control, disease-free survival (DFS), and overall survival (OS) rate was 93% (95% confidence interval [CI] 87-99%), 79% (95% CI 69-89%), and 74% (95% CI 64-85%), respectively. No significant difference in outcome was found between Groups 1 and 2. The 5-year vaginal/pelvic control rate was 97% (95% CI 91-100%) in Group 1 compared with 90% (95% CI 81-99%) in Group 2 (p = 0.2). The 5-year DFS rate was 79% (95% CI 64-95%) in Group 1 vs. 78% (95% CI 65-92%) in Group 2 (p = 0.6), and the 5-year OS rate was 71% (95% CI 55-87%) in Group 1 vs. 79% (95% CI 66-92%) in Group 2 (p = 0.3). The influence on outcome of age, race, comprehensive surgical staging, CSLI, amount of myometrial invasion, cervical involvement, lower uterine segment involvement, and presence of pure PS or CC histologic features was evaluated. On multivariate analysis, only CSLI correlated with poor DFS (p = 0.04; relative risk 3, 95% CI 1-9) and OS (p = 0.02; relative risk 3, 95% CI 1-6). CONCLUSION: On the basis of the results of this study, no significant difference in outcome exists between patients with Stage I-II endometrial cancer with PS/CC histologic features and those with similar stage disease, but with FIGO Grade 3 endometrioid histologic features. CSLI was the only independent predictor of poor DFS and OS.

Adult↗

PubMed2002

The significance of the amount of myometrial invasion in patients with Stage IB endometrial carcinoma.

BACKGROUND: The 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma defined Stage IB as disease with invasion of less than one-half of the myometrium, although most of the data on prognostic factors are based on invasion of the inner one-third, middle one-third, or outer one-third of the myometrium. The objective of this study was to determine whether the depth of myometrial invasion is correlated with outcome in patients with Stage IB endometrial carcinoma. METHODS: Between November, 1987 and June, 1998, 251 patients with Stage IB endometrioid adenocarcinoma of the uterus underwent simple hysterectomy followed by intravaginal brachytherapy. The depth of myometrial invasion was less than or equal to one-third (Group I) in 191 of 251 patients (79%) and greater than one-third to less than one-half (Group II) in 52 of 251 patients (21%). Comprehensive surgical staging (CSS) was done in 12% of patients. The two groups were balanced with regard to age (< 60 years vs. > or = 60 years), FIGO grade, lower uterine segment involvement (LUSI), CSS, and the use of postoperative external-beam radiation. The rate of capillary-like space invasion (CLSI), however, was 9% in Group I compared with 25% in Group II (P = 0.002). The median follow-up was 58 months. RESULTS: The overall 5-year actuarial local-regional control (LRC), disease free (DFS) survival, and overall survival (OS) rates were 95%, 92%, and 92%, respectively. These end points, however, did not vary significantly between the two groups. The 5-year LRC, DFS, and OS rates in Groups I and II were 96% versus 95%, respectively (P = 0.9); 92% versus 94%, respectively (P = 0.7); and 92% versus 90%, respectively (P = 0.5). On multivariate analysis, the influence on outcome of age, grade, amount of myometrial invasion, LUSI, and CLSI was evaluated. Only age > or = 60 years and FIGO Grade 3 were correlated with poor DFS (P = 0.02 and P = 0.03, respectively) and OS (P = 0.001 and P = 0.01, respectively). CONCLUSIONS: Based on this study, in patients with Stage IB endometrial carcinoma, the amount of myometrial invasion, defined as invasion less than or equal to one-third of the myometrium versus invasion greater than one-third and less than one-half of the myometrium, did not appear to influence outcome. Age > or = 60 years and FIGO Grade 3, however, emerged as independent prognostic factors for poor DFS and OS.

Adenocarcinoma↗

PubMed2002

Intravaginal high-dose-rate brachytherapy for Stage IB (FIGO Grade 1, 2) endometrial cancer.

PURPOSE: To evaluate the outcome of patients with Stage IB Grades 1 and 2 endometrial cancer treated with adjuvant high-dose-rate intravaginal brachytherapy. METHODS AND MATERIALS: Between November 1987 and October 1999, 233 patients with Stage IB FIGO Grades 1 and 2 were treated with postoperative adjuvant high-dose-rate intravaginal brachytherapy. The median dose was 21 Gy in 7 Gy/fraction given at 2-week intervals. The mean age was 60 years. All patients underwent simple hysterectomy. Comprehensive surgical staging, defined as pelvic washing and pelvic and paraaortic lymph nodes sampling, was done in 9% of patients. Patients with FIGO Grade 3, papillary serous cancer, or clear-cell cancer were excluded from this analysis. Complications were assessed in terms of late Radiation Therapy Oncology Group toxicity (Grade > or =3) of the gastrointestinal tract, genitourinary tract, and vagina. RESULTS: With a median follow-up of 57 months, the 5-year vaginal/pelvic control, disease-free survival, and overall survival rate was 96% (95% confidence interval [CI] 94-99%), 94% (95% CI 91-98%), and 94% (95% CI 91-98%), respectively. The influence on outcome of age, grade (1 vs. 2), depth of invasion (one-third or less or greater than one-third), capillary space-like invasion, lower uterine segment involvement, and comprehensive surgical staging was evaluated. None of these factors significantly affected the rate of vaginal/pelvic control. Only age > or =60 years influenced the outcome for disease-free and overall survival. The 5-year rate for both disease-free and overall survival was 90% (95% CI 84-97%) for patients > or =60 years old compared with 99% (95% CI 96-100%) for those <60 years (p = 0.03 and 0.005, respectively). Of 233 patients, 3 (1%) developed Grade 3 or greater complications, with a 5-year actuarial rate of 2% (95% CI 0-5%). Two patients developed Grade 3 genitourinary toxicity, and 1 Grade 4 vaginal toxicity. CONCLUSION: On the basis of this retrospective study, adjuvant postoperative high-dose-rate intravaginal brachytherapy provides excellent outcomes and acceptable morbidity. These results compare very favorably with those reported in the literature using surgery alone or with pelvic radiation.

Adult↗